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Wu C, Qiao Y, Zhang L, Wang C, Chen J, Chen C, Xu C, Tsai TY, Xu J, Zhao J. Effects of Biceps Rerouting on In Vivo Glenohumeral Kinematics in the Treatment of Large-to-Massive Rotator Cuff Tears. Am J Sports Med 2025; 53:427-436. [PMID: 39748800 DOI: 10.1177/03635465241301778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
BACKGROUND Arthroscopic repair with the biceps rerouting (BR) technique has been determined to lead to promising clinical and biomechanical outcomes for treating large-to-massive rotator cuff tears (LMRCTs). However, the in vivo effects of BR on glenohumeral kinematics during functional shoulder movements have not been fully elucidated. PURPOSE To investigate whether BR provides a better restoration of shoulder kinematics compared with conventional rotator cuff repair (RCR). STUDY DESIGN Controlled laboratory study. METHODS Patients who underwent either repair with the BR technique (BR group) or RCR alone (RCR group) for treating LMRCTs between January 2021 and May 2022 were enrolled. They underwent a 1-year postoperative kinematic evaluation of bilateral shoulders by performing scapular-plane abduction with a dual fluoroscopic imaging system. Glenohumeral translation in the superior-inferior (S-I) and anterior-posterior (A-P) directions was assessed in shoulder abduction at 10° increments. Moreover, the mean, maximum, minimum, and range of glenohumeral translation were calculated throughout the entire movement. RESULTS A total of 9 patients were enrolled in each group for final analysis, and baseline characteristics were comparable between the groups. In the RCR group, compared with contralateral shoulders, the operative shoulders showed increased superior humeral head translation during lower abduction angles of 30° to 50° (all P≤ .004), with a greater maximum (P = .014) and a larger range (P = .002) for S-I translation throughout the entire movement. In the BR group, no significant differences between operative and contralateral shoulders were detected in any kinematic variables for S-I translation (all P≥ .132); however, the operative shoulders exhibited a larger maximum (P = .031), a smaller minimum (P = .008), and a larger range (P < .001) for A-P translation throughout the entire movement compared with the contralateral shoulders. CONCLUSION BR successfully reduced residual superior humeral head translation compared with conventional RCR and restored normal S-I glenohumeral kinematics in the treatment of LMRCTs. However, A-P glenohumeral kinematics was not fully restored after BR, and its effect on long-term clinical outcomes requires further investigation. CLINICAL RELEVANCE BR can be a promising technique to treat LMRCTs. However, its potential adverse effects on A-P glenohumeral kinematics should not be ignored, requiring further clinical evidence to determine long-term outcomes.
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Affiliation(s)
- Chenliang Wu
- Department of Sports Medicine, Shanghai Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yi Qiao
- Department of Sports Medicine, Shanghai Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ling Zhang
- Shanghai University of Sport, Shanghai, China
| | - Cong Wang
- Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Jiebo Chen
- Department of Sports Medicine, Shanghai Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chang'an Chen
- Department of Sports Medicine, Shanghai Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Caiqi Xu
- Department of Sports Medicine, Shanghai Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Tsung-Yuan Tsai
- Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Junjie Xu
- Department of Sports Medicine, Shanghai Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jinzhong Zhao
- Department of Sports Medicine, Shanghai Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Gibbons MC, Silldorff M, Okuno H, Esparza MC, Migdal C, Johnson S, Schenk S, Ward SR. The effect of tenotomy, neurotomy, and dual injury on mouse rotator cuff muscles: Consequences for the mouse as a preclinical model. J Orthop Res 2024; 42:1170-1179. [PMID: 38245849 DOI: 10.1002/jor.25786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 12/13/2023] [Accepted: 01/03/2024] [Indexed: 01/22/2024]
Abstract
A common animal model of muscle pathology following rotator cuff tear (RCT) is a tenotomy of the supraspinatus and infraspinatus, often combined with neurotomy of the suprascapular nerve, which induces a more robust atrophy response than tenotomy alone. However, the utility of this model depends on its similarity to human muscle pathology post-RCT, both in terms of the disease phenotype and mechanisms of muscle atrophy and fatty infiltration. Given the clinical prevalence of nerve injury is low and the muscular response to denervation is distinct from mechanical unloading in other models, an understanding of the biological influence of the nerve injury is critical for interpreting data from this RCT model. We evaluated the individual and combined effect of tenotomy and neurotomy across multiple biological scales, in a robust time-series in the mouse supraspinatus. Muscle composition, histological, and gene expression data related to muscle atrophy, degeneration-regeneration, fatty infiltration, and fibrosis were evaluated. Broadly, we found tenotomy alone caused small, transient changes in these pathological features, which resolved over the course of the study, while neurotomy alone caused a significant fatty atrophy phenotype. The dual injury group had a similar fatty atrophy phenotype to the neurotomy group, though the addition of tenotomy did marginally enhance the fat and connective tissue. Overall, these results suggest the most clinically relevant injury model, tenotomy alone, does not produce a clinically relevant phenotype. The dual injury model partially recapitulates the human condition, but it does so through a nerve injury, which is not well justified clinically.
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Affiliation(s)
- Michael C Gibbons
- Department of Bioengineering, University of California San Diego, San Diego, California, USA
| | - Morgan Silldorff
- Department of Orthopaedic Surgery, University of California San Diego, San Diego, California, USA
| | - Hiroshi Okuno
- Department of Orthopaedic Surgery, University of California San Diego, San Diego, California, USA
| | - Mary C Esparza
- Department of Orthopaedic Surgery, University of California San Diego, San Diego, California, USA
| | - Christopher Migdal
- Department of Orthopaedic Surgery, University of California San Diego, San Diego, California, USA
| | - Seth Johnson
- Department of Orthopaedic Surgery, University of California San Diego, San Diego, California, USA
| | - Simon Schenk
- Department of Orthopaedic Surgery, University of California San Diego, San Diego, California, USA
| | - Samuel R Ward
- Department of Orthopaedic Surgery, University of California San Diego, San Diego, California, USA
- Department of Radiology, University of California San Diego, San Diego, California, USA
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Kim HG, Kim SC, Park JH, Kim JS, Kim DY, Lee SM, Yoo JC. Clinical and Structural Outcomes of Arthroscopic Rotator Cuff Repair in Patients Over 75 Years Are Comparable to Those in Younger Patients: A Propensity Score-Matched Comparative Study. Arthroscopy 2024; 40:1739-1750. [PMID: 37952745 DOI: 10.1016/j.arthro.2023.10.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 10/18/2023] [Accepted: 10/25/2023] [Indexed: 11/14/2023]
Abstract
PURPOSE To compare clinical and structural outcomes of arthroscopic rotator cuff repair (ARCR) in patients over 75 years and those under 75 years and to analyze the factors associated with retear and clinical outcomes after ARCR. METHODS This retrospective study reviewed patients who underwent ARCR between 2011 and 2021 with at least 2 years of follow-up. Using propensity score matching for sex, tear size, subscapularis involvement, and follow-up time, this study included 54 patients older than 75 years (group A) and 54 patients younger than 75 years (group B). Cuff integrity was evaluated using magnetic resonance imaging (MRI). Structural and clinical outcomes were compared between the 2 groups. RESULTS The mean improvements in external rotation (P = .030) and the American Shoulder and Elbow Surgeons (ASES) score (P = .043) were significantly higher in group A. Visual analog scales for pain and function, ASES score, and Constant score were significantly improved in both groups (all P = .001). On routine postoperative MRI at 6 months, the retear rate was 20.4% (11/54) in group A and 18.5% (10/54) in group B with no statistical difference between the 2 groups (P = .808). Factor analysis in group A showed that follow-up duration (P = .019), tear size in mediolateral dimension (P = .037), occupation ratio (P = .036), and incomplete repair (P = .034) were associated with retear, and mild glenohumeral arthritis (P = .003) and subscapularis involvement (P = .018) were associated with inferior Constant score. CONCLUSIONS Clinical and structural outcomes after ARCR in patients aged 75 years or older are comparable to those in patients younger than 75 years. LEVEL OF EVIDENCE Level III, retrospective case-control study.
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Affiliation(s)
- Hyun Gon Kim
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
| | - Su Cheol Kim
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
| | - Jong Hun Park
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
| | - Jae Soo Kim
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
| | - Dae Yeung Kim
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
| | - Sang Min Lee
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
| | - Jae Chul Yoo
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
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Tong Z, Li H, Jin Y, Sheng L, Ying M, Liu Q, Wang C, Teng C. Mechanisms of ferroptosis with immune infiltration and inflammatory response in rotator cuff injury. Genomics 2023; 115:110645. [PMID: 37230182 DOI: 10.1016/j.ygeno.2023.110645] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 04/03/2023] [Accepted: 05/19/2023] [Indexed: 05/27/2023]
Abstract
The processes driving ferroptosis and rotator cuff (RC) inflammation are yet unknown. The mechanism of ferroptosis and inflammation involved in the development of RC tears was investigated. The Gene Expression Omnibus database was used to obtain the microarray data relevant to the RC tears for further investigation. In this study, we created an RC tears rat model for in vivo experimental validation. For the additional function enrichment analysis, 10 hub ferroptosis-related genes were chosen to construct the correlation regulation network. In RC tears, it was discovered that genes related to hub ferroptosis and hub inflammatory response were strongly correlated. The outcomes of in vivo tests showed that RC tears were related to Cd68-Cxcl13, Acsl4-Sat1, Acsl3-Eno3, Acsl3-Ccr7, and Ccr7-Eno3 pairings in regulating ferroptosis and inflammatory response. Thus, our results show an association between ferroptosis and inflammation, providing a new avenue to explore the clinical treatment of RC tears.
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Affiliation(s)
- Zhicheng Tong
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 32200, China
| | - Huimin Li
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 32200, China
| | - Yanglei Jin
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 32200, China
| | - Lingchao Sheng
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 32200, China
| | - Mingshuai Ying
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 32200, China
| | - Qixue Liu
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 32200, China
| | - Chenhuan Wang
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 32200, China
| | - Chong Teng
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 32200, China..
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Xu J, Liu B, Han K, Ye Z, Zhang X, Qiao Y, Jin Y, Jiang J, Su W, Li Y, Zhao J. The Modified Assessment Tool Based on Scapular Y-View for Global Fatty Infiltration in the Supraspinatus Muscle: Correlation, Predictive Performance, and Reliability Analyses. Am J Sports Med 2023; 51:1243-1254. [PMID: 36917780 DOI: 10.1177/03635465231158372] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
BACKGROUND The accurate evaluation of rotator cuff (RC) fatty degeneration after tears is critical for appropriate surgical decision making and prognosis. However, there is currently no reliable and practical tool to reflect the global fatty infiltration (Global-FI) throughout the 3-dimensional (3D) volumetric RC muscles. PURPOSE (1) To determine the correlations between 2 modified assessment tools and the Global-FI and their predictive performances and reliabilities for Global-FI prediction, and (2) to compare these predictive parameters with those of the conventional tool using a single scapular Y-view slice. STUDY DESIGN Cohort study (diagnosis); Level of evidence, 3. METHODS A total of 49 patients with full-thickness RC tears scheduled to undergo arthroscopic repairs were included, and their surgical shoulders underwent 6-point Dixon magnetic resonance imaging preoperatively. The Global-FI was measured by calculating the 3D-volumetric fat fraction (FF) of the whole supraspinatus muscle through all acquired oblique sagittal slices. As a commonly used radiological landmark, the scapular Y-view was used to evaluate single-plane fatty infiltration (Y-FI) by calculating the FF in 1 slice, defined as the conventional assessment tool. Two modified assessment tools expand the analytic imaging by integrating the FFs from the scapular Y-view slice and its neighboring slices, which were calculated by averaging the FFs of these 3 slices (meanY3-FI) and accumulating local 3D-volumetric FFs from 3 slices (volY3-FI), respectively. The correlations between 3 assessment tools and the Global-FI were analyzed, and the predictive performance for Global-FI prediction using these tools was determined by goodness of fit and agreement. Moreover, the inter- and intraobserver reliabilities of these assessment tools were evaluated. Similar analyses were performed in the small-medium, large, or massive tear subgroups. RESULTS The Y-FI was significantly higher than the Global-FI in all cases and tear size subgroups, while the 2 modified assessment tools (meanY3-FI and volY3-FI) did not significantly differ from the Global-FI. All assessment tools were significantly correlated with the Global-FI, but the meanY3-FI and volY3-FI showed stronger correlations than the Y-FI, which was also determined in different tear sizes. Moreover, the regression models of the meanY3-FI and volY3-FI showed superior goodness of fit to Y-FI in Global-FI prediction in all cases and subgroups, with larger coefficients of determination (R2) and smaller root mean square errors. The predicted Global-FI using the regression model of volY3-FI had the best agreement with the measured Global-FI, followed by the meanY3-FI, both showing smaller biases and standard deviation of the percentage difference between predicted- and measured Global-FI than the conventional Y-FI. In addition, the 2 modified assessment tools achieved better interobserver and intraobserver reliabilities than the conventional tool in all cases and subgroups. CONCLUSION Two modified assessment tools (meanY3-FI and volY3-FI) were comparable with the Global-FI of the whole supraspinatus muscle, showing stronger correlations with the Global-FI and better predictive performances and reliabilities than the conventional tool (Y-FI). Moreover, the volY3-FI was slightly superior to meanY3-FI in the predictive performance and reliability.
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Affiliation(s)
- Junjie Xu
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Beibei Liu
- Institute of Diagnostic and Interventional Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kang Han
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zipeng Ye
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiuyuan Zhang
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi Qiao
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuchen Jin
- Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Department of Nuclear Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.,Human Oncology and Pathogenesis, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
| | - Jia Jiang
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Su
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuehua Li
- Institute of Diagnostic and Interventional Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinzhong Zhao
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Künzler MB, McGarry MH, Akeda M, Ihn H, Karol A, von Rechenberg B, Schär MO, Zumstein MA, Lee TQ. Effect of PARP-1 Inhibition on Rotator Cuff Healing: A Feasibility Study Using Veliparib in a Rat Model of Acute Rotator Cuff Repair. Am J Sports Med 2023; 51:758-767. [PMID: 36745049 DOI: 10.1177/03635465221148494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND PARP-1 (poly[ADP-ribose]) was shown to influence the inflammatory response after rotator cuff tear, leading to fibrosis, muscular atrophy, and fatty infiltration in mouse rotator cuff degeneration. So far, it is not known how PARP-1 influences enthesis healing after rotator cuff tear repair. HYPOTHESIS/PURPOSE This study aimed to examine the feasibility of oral PARP-1 inhibition and investigate its influence on rat supraspinatus enthesis and muscle healing after rotator cuff repair. The hypothesis was that oral PARP-1 inhibition would improve enthesis healing after acute rotator cuff repair in a rat model. STUDY DESIGN Controlled laboratory study. METHODS In 24 Sprague-Dawley rats, the supraspinatus tendon was sharply detached and immediately repaired with a single transosseous suture. The rats were randomly allocated into 2 groups, with the rats in the inhibitor group receiving veliparib with a target dose of 12.5 mg/kg/d via drinking water during the postoperative recovery period. The animals were sacrificed 8 weeks after surgery. For the analysis, macroscopic, biomechanical, and histologic methods were used. RESULTS Oral veliparib was safe for the rats, with no adverse effects observed. In total, the inhibitor group had a significantly better histologic grading of the enthesis with less scar tissue formation. The macroscopic cross-sectional area of the supraspinatus muscles was 10.5% higher (P = .034) in the inhibitor group, which was in agreement with an 8.7% higher microscopic muscle fiber diameter on histologic sections (P < .0001). There were no statistically significant differences in the biomechanical properties between the groups. CONCLUSION This study is the first to investigate the influence of PARP-1 inhibition on healing enthesis. On the basis of these findings, we conclude that oral veliparib, which was previously shown to inhibit PARP-1 effectively, is safe to apply and has beneficial effects on morphologic enthesis healing and muscle fiber size. CLINICAL RELEVANCE Modulating the inflammatory response through PARP-1 inhibition during the postoperative healing period is a promising approach to improve enthesis healing and reduce rotator cuff retearing. With substances already approved by the Food and Drug Administration, PARP-1 inhibition bears high potential for future translation into clinical application.
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Affiliation(s)
- Michael B Künzler
- Shoulder, Elbow and Orthopaedic Sports Medicine, Inselspital University Hospital Bern, University of Bern, Bern, Switzerland.,Orthopaedics Biomechanics Laboratory, VA Long Beach Healthcare System, Long Beach, California, USA.,Musculoskeletal Research Unit, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Michelle H McGarry
- Orthopaedics Biomechanics Laboratory, VA Long Beach Healthcare System, Long Beach, California, USA.,Orthopaedics Biomechanics Laboratory, Congress Medical Foundation, Pasadena, California, USA
| | - Masaki Akeda
- Orthopaedics Biomechanics Laboratory, VA Long Beach Healthcare System, Long Beach, California, USA
| | - Hansel Ihn
- Orthopaedics Biomechanics Laboratory, VA Long Beach Healthcare System, Long Beach, California, USA
| | - Agnieszka Karol
- Musculoskeletal Research Unit, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | | | - Michael O Schär
- Shoulder, Elbow and Orthopaedic Sports Medicine, Inselspital University Hospital Bern, University of Bern, Bern, Switzerland
| | - Matthias A Zumstein
- Shoulder, Elbow and Orthopaedic Sports Medicine, Inselspital University Hospital Bern, University of Bern, Bern, Switzerland.,Shoulder, Elbow and Orthopaedic Sports Medicine, Sonnenhof Orthopaedics, Bern, Switzerland
| | - Thay Q Lee
- Orthopaedics Biomechanics Laboratory, VA Long Beach Healthcare System, Long Beach, California, USA.,Orthopaedics Biomechanics Laboratory, Congress Medical Foundation, Pasadena, California, USA
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Dysfunctional paraspinal muscles in adult spinal deformity patients lead to increased spinal loading. EUROPEAN SPINE JOURNAL 2022; 31:2383-2398. [PMID: 35842491 PMCID: PMC9288260 DOI: 10.1007/s00586-022-07292-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 05/17/2022] [Accepted: 06/06/2022] [Indexed: 11/18/2022]
Abstract
Purpose Decreased spinal extensor muscle strength in adult spinal deformity (ASD) patients is well-known but poorly understood; thus, this study aimed to investigate the biomechanical and histopathological properties of paraspinal muscles from ASD patients and predict the effect of altered biomechanical properties on spine loading. Methods 68 muscle biopsies were collected from nine ASD patients at L4–L5 (bilateral multifidus and longissimus sampled). The biopsies were tested for muscle fiber and fiber bundle biomechanical properties and histopathology. The small sample size (due to COVID-19) precluded formal statistical analysis, but the properties were compared to literature data. Changes in spinal loading due to the measured properties were predicted by a lumbar spine musculoskeletal model. Results Single fiber passive elastic moduli were similar to literature values, but in contrast, the fiber bundle moduli exhibited a wide range beyond literature values, with 22% of 171 fiber bundles exhibiting very high elastic moduli, up to 20 times greater. Active contractile specific force was consistently less than literature, with notably 24% of samples exhibiting no contractile ability. Histological analysis of 28 biopsies revealed frequent fibro-fatty replacement with a range of muscle fiber abnormalities. Biomechanical modelling predicted that high muscle stiffness could increase the compressive loads in the spine by over 500%, particularly in flexed postures. Discussion The histopathological observations suggest diverse mechanisms of potential functional impairment. The large variations observed in muscle biomechanical properties can have a dramatic influence on spinal forces. These early findings highlight the potential key role of the paraspinal muscle in ASD.
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Anti-inflammatory and Tendon-Protective Effects of Adipose Stem Cell-Derived Exosomes with Concomitant Use of Glucocorticoids. Stem Cells Int 2022; 2022:1455226. [PMID: 35646125 PMCID: PMC9142315 DOI: 10.1155/2022/1455226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 04/21/2022] [Accepted: 04/29/2022] [Indexed: 11/30/2022] Open
Abstract
Glucocorticoid (GC) injections are commonly used in clinical practice to relieve pain and improve function in patients with multiple shoulder disabilities but cause detrimental effects on rotator cuff tendons. Adipose stem cell-derived exosomes (ASC-Exos) reportedly recover impaired tendon matrix metabolism by maintaining tissue homeostasis. However, it is unclear whether additional treatment with ASC-Exos overrides the detrimental effects of GCs without interfering with their anti-inflammatory effects. Thus, we aimed to investigate the anti-inflammatory effect of ASC-Exos with GCs and protective effect of ASC-Exos against GC-induced detriments. The present study comprised in vitro and in vivo studies. In vitro inflammatory analysis revealed that ASC-Exos exerted a synergic anti-inflammatory effect with GCs by significantly decreasing secretion of proinflammatory cytokines by RAW cells and increasing secretion of anti-inflammatory cytokines. In vitro cytoprotective analysis showed that ASC-Exos overrode GC-induced detrimental effects on tenocytes by significantly improving GC-suppressed cellular proliferation, migration, and transcription of tenocytic matrix molecules and degradative enzyme inhibitors and significantly decreasing GC-induced cell senescence, apoptosis, and transcription of ROS and tenocytic degradative enzymes. In vivo studies revealed that additional ASC-Exo injection restored impairments in histological and biomechanical properties owing to GC administration. Collectively, these results suggest that ASC-Exos exert a stronger anti-inflammatory effect in combination with GCs, overriding their detrimental effects on rotator cuff tendons.
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Geometric modeling predicts architectural adaptations are not responsible for the force deficit following tenotomy in the rotator cuff. J Biomech 2022; 138:111105. [DOI: 10.1016/j.jbiomech.2022.111105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 04/18/2022] [Accepted: 04/24/2022] [Indexed: 10/18/2022]
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Vargas-Vila MA, Gibbons MC, Wu IT, Esparza MC, Kato K, Johnson SD, Masuda K, Ward SR. Progression of muscle loss and fat accumulation in a rabbit model of rotator cuff tear. J Orthop Res 2022; 40:1016-1025. [PMID: 34392563 PMCID: PMC8844305 DOI: 10.1002/jor.25160] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 06/09/2021] [Accepted: 07/30/2021] [Indexed: 02/04/2023]
Abstract
Rotator cuff (RC) tears present a treatment challenge due to muscle atrophy and degeneration, fatty infiltration, and fibrosis. The purpose of this study was to generate a high time-resolution model of RC tear in rabbits and to characterize the progression of architectural and histological changes. Thirty-five female New Zealand White rabbits (age: 6 months) underwent left supraspinatus tenotomy. Five rabbits were used to evaluate immediate muscle architectural changes. The remaining 30 rabbits underwent right shoulder sham surgery and sacrifice at 1, 2, 4, 8, or 16 weeks. Histology was used to quantify muscle fiber cross-sectional area (CSA), muscle degeneration and regeneration, and fat localized to inter- versus intrafascicular regions. Muscle fiber CSA decreased by 26.5% compared to sham at 16 weeks (effect of treatment, p < 0.0001). Muscle degeneration increased after tenotomy (effect of treatment, p = 0.0006) without any change in regeneration. Collagen and fat content increased by 4 weeks and persisted through 16 weeks. Interfascicular fat was increased at all time points, but intrafascicular fat was increased only at 1, 4, and 16 weeks posttenotomy. Intrafascicular fat adjacent to degenerating muscle fibers increased as well (effect of treatment, p < 0.0001; effect of time, p = 0.0102). Statement of clinical relevance: Rabbit supraspinatus tenotomy recapitulates key features of the pathophysiology of human RC tears, including muscle atrophy and degeneration, lack of regeneration, fat accumulation, and fibrosis.
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Affiliation(s)
| | | | - Isabella T. Wu
- Department of Orthopaedic Surgery, UC San Diego, La Jolla CA, USA
| | - Mary C. Esparza
- Department of Orthopaedic Surgery, UC San Diego, La Jolla CA, USA
| | - Kenji Kato
- Department of Orthopaedic Surgery, Nagoya City University, Nagoya, Japan
| | - Seth D. Johnson
- Department of Orthopaedic Surgery, UC San Diego, La Jolla CA, USA
| | - Koichi Masuda
- Department of Orthopaedic Surgery, UC San Diego, La Jolla CA, USA
| | - Samuel R. Ward
- Department of Orthopaedic Surgery, UC San Diego, La Jolla CA, USA,Department of Bioengineering, UC San Diego, La Jolla CA, USA,Department of Radiology, UC San Diego, La Jolla CA, USA
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11
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Yu JS, Dare DM, Edon D, Sinatro AL, Sarver DC, Rodeo S, Dines JS, Mendias CL. Shoulder Lesions Do Not Increase Inflammatory Biomarkers in Patients Undergoing Surgery for Glenohumeral Instability: An Exploratory Study. TRANSLATIONAL SPORTS MEDICINE 2022; 2022:4220356. [PMID: 38655158 PMCID: PMC11022782 DOI: 10.1155/2022/4220356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 02/10/2022] [Indexed: 04/26/2024]
Abstract
Circulating protein biomarkers have demonstrated utility as a diagnostic tool in predicting musculoskeletal disease severity, but their utility in the evaluation of shoulder lesions associated with shoulder instability is unknown. Thus, the purpose of this exploratory study was to determine whether preoperative biomarkers of cartilage turnover and inflammation are associated with specific shoulder lesions in shoulder instability. Thirty-three patients (29.9 ± 9.4 years of age, 4.5 ± 4.7 dislocations) undergoing surgical treatment for shoulder instability were assessed for the presence or absence of associated shoulder lesions. Biomarkers including cartilage oligomeric matrix protein (COMP), C-reactive protein (HS-CRP), interleukin-8 (IL-8), and macrophage inflammatory protein-1β (MIP-1b) were collected at the time of surgery. Patients with Hill-Sachs lesions had a 31% increase in COMP plasma levels (p=0.046). No other significant differences were observed for COMP, HS-CRP, IL-8, and MIP-1b with any shoulder lesion including Hill-Sachs lesions, capsular injuries, bony Bankart lesions, and SLAP lesions. In conclusion, inflammatory biomarkers including HS-CRP, IL-8, and MIP-1b were not associated with specific shoulder lesions, while biomarkers of cartilage turnover (COMP) were only elevated in Hill-Sachs lesions. These findings suggest that these biomarkers may have limited utility as prognostic indicators in patients with shoulder instability, though large-scale and longitudinal studies are still necessary.
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Affiliation(s)
- Jonathan S. Yu
- Hospital for Special Surgery, New York, NY, USA
- Weill Cornell Medicine, New York, NY, USA
| | - David M. Dare
- Hospital for Special Surgery, New York, NY, USA
- Raleigh Orthopedic Clinic, Raleigh, NC, USA
| | - Daniel Edon
- Hospital for Special Surgery, New York, NY, USA
| | - Alec L. Sinatro
- Hospital for Special Surgery, New York, NY, USA
- Albert Einstein College of Medicine, New York, NY, USA
| | - Dylan C. Sarver
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Scott Rodeo
- Hospital for Special Surgery, New York, NY, USA
- Weill Cornell Medicine, New York, NY, USA
| | - Joshua S. Dines
- Hospital for Special Surgery, New York, NY, USA
- Weill Cornell Medicine, New York, NY, USA
| | - Christopher L. Mendias
- Hospital for Special Surgery, New York, NY, USA
- Weill Cornell Medicine, New York, NY, USA
- Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA
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12
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Wang S, Ying JH, Xu H. Identification of Diagnostic Biomarkers Associated with Stromal and Immune Cell Infiltration in Fatty Infiltration After Rotator Cuff Tear by Integrating Bioinformatic Analysis and Machine-Learning. Int J Gen Med 2022; 15:1805-1819. [PMID: 35221715 PMCID: PMC8865865 DOI: 10.2147/ijgm.s354741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 02/11/2022] [Indexed: 11/26/2022] Open
Abstract
Purpose The present study aimed to explore potential diagnostic biomarkers for fatty infiltration (FI) of the rotator cuff muscles after rotator cuff tear (RCT) and investigate the influence of stromal and immune cell infiltration on this pathology. Methods The GSE130447 and GSE103266 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified, and gene set enrichment analyses were performed by R software. Two machine learning algorithms, random forest and multiple support vector machine recursive feature elimination (mSVM-RFE), were used to screen candidate biomarkers. The diagnostic value of the screened biomarkers was further validated by the area under the ROC curve (AUC) in the GSE103266 dataset. Murine microenvironment cell population counter (mMCP-counter) method was employed to estimate stromal and immune cell infiltration of FI. The correlation between biomarkers and infiltrated immune and stromal cell subsets was further analyzed. Results A total of 2123 DEGs were identified. The identified DEGs were predominantly linked to immune system process, extracellular matrix organization and PPAR signalling pathway. FABP5 (AUC = 0.958) and MGP (AUC = 1) were screened as diagnostic biomarkers of FI. Stromal and immune cell infiltration analysis showed that monocytes, mast cells, vessels, endothelial cells and fibroblasts may be related to the process of FI. FABP5 and MGP were positively correlated with vessels whereas negatively correlated with monocytes and mast cells. Conclusion FABP5 and MGP can serve as diagnostic biomarkers of FI after RCT, and stromal and immune cell infiltration may play a crucial role in this pathology.
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Affiliation(s)
- Si Wang
- Department of Information Centre, Lishui Hospital, Zhejiang University School of Medicine, Lishui, 323000, Zhejiang, People’s Republic of China
| | - Jin-He Ying
- Department of Joint Surgery, Lishui Hospital, Zhejiang University School of Medicine, Lishui, 323000, Zhejiang, People’s Republic of China
| | - Huan Xu
- Department of Joint Surgery, Lishui Hospital, Zhejiang University School of Medicine, Lishui, 323000, Zhejiang, People’s Republic of China
- Correspondence: Huan Xu, Tel +86 578 2285310, Fax +865782133457, Email
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13
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Hyman SA, Wu IT, Vasquez-Bolanos LS, Norman MB, Esparza MC, Bremner SN, Dorn SN, Ramirez I, Fithian DC, Lane JG, Singh A, Ward SR. Supraspinatus muscle architecture and physiology in a rabbit model of tenotomy and repair. J Appl Physiol (1985) 2021; 131:1708-1717. [PMID: 34647843 PMCID: PMC8828274 DOI: 10.1152/japplphysiol.01119.2020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 09/20/2021] [Accepted: 10/11/2021] [Indexed: 11/22/2022] Open
Abstract
Chronic rotator cuff tears can cause severe functional deficits. Addressing the chronic fatty and fibrotic muscle changes is of high clinical interest; however, the architectural and physiological consequences of chronic tear and repair are poorly characterized. We present a detailed architectural and physiological analysis of chronic tear and repair (both over 8 and 16 wk) compared with age-matched control rabbit supraspinatus (SSP) muscles. Using female New Zealand White Rabbits (n = 30, n = 6/group) under 2% isoflurane anesthesia, the SSP was surgically isolated and maximum isometric force was measured at four to six muscle lengths. Architectural analysis was performed, and maximum isometric stress was computed. Whole muscle length-tension curves were generated using architectural measurements to compare experimental physiology to theoretical predictions. Architectural measures are consistent with persistent radial and longitudinal atrophy over time in tenotomy that fails to recover after repair. Maximum isometric force was significantly decreased after 16 wk tenotomy and not significantly improved after repair. Peak isometric force reported here are greater than prior reports of rabbit SSP force after tenotomy. Peak stress was not significantly different between groups and consistent with prior literature of SSP stress. Muscle strain during contraction was significantly decreased after 8 wk of tenotomy and repair, indicating effects of tear and repair on muscle function. The experimental length-tension data were overlaid with predicted curves for each experimental group (generated from structural data), exposing the altered structure-function relationship for tenotomy and repair over time. Data presented here contribute to understanding the physiological implications of disease and repair in the rotator cuff.NEW & NOTEWORTHY We utilize an established method to measure the length-tension relationship for the rabbit supraspinatus in normal, torn, and repaired muscles. We then perform architectural analysis to evaluate structural changes after tear and repair. Although peak isometric force is lower in the tear and repair groups, there are no differences in peak stresses across groups. These findings indicate persistent structural changes (both radial and longitudinal atrophy) and physiological deficiencies (decreased peak force and uncoupling structure-function relationship) after tenotomy that do not significantly recover after repair.
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Affiliation(s)
- Sydnee A Hyman
- Department of Bioengineering, University of California, San Diego, California
- Department of Orthopaedic Surgery, University of California, San Diego, California
| | - Isabella T Wu
- Department of Orthopaedic Surgery, University of California, San Diego, California
| | - Laura S Vasquez-Bolanos
- Department of Bioengineering, University of California, San Diego, California
- Department of Orthopaedic Surgery, University of California, San Diego, California
| | - Mackenzie B Norman
- Department of Orthopaedic Surgery, University of California, San Diego, California
- Dartmouth Geisel School of Medicine, Hanover, New Hampshire
| | - Mary C Esparza
- Department of Orthopaedic Surgery, University of California, San Diego, California
| | - Shannon N Bremner
- Department of Orthopaedic Surgery, University of California, San Diego, California
| | - Shanelle N Dorn
- Department of Orthopaedic Surgery, University of California, San Diego, California
| | - Ivan Ramirez
- Department of Orthopaedic Surgery, University of California, San Diego, California
| | - Donald C Fithian
- Department of Orthopaedic Surgery, University of California, San Diego, California
| | - John G Lane
- Department of Orthopaedic Surgery, University of California, San Diego, California
| | - Anshuman Singh
- Department of Orthopaedic Surgery, University of California, San Diego, California
- Department of Orthopaedic Surgery, Kaiser Permanente, San Diego, California
| | - Samuel R Ward
- Department of Bioengineering, University of California, San Diego, California
- Department of Orthopaedic Surgery, University of California, San Diego, California
- Department of Radiology, University of California, San Diego, California
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14
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Sakaki Y, Taniguchi K, Katayose M, Kura H, Okamura K. Effects of shoulder abduction on the stiffness of supraspinatus muscle regions in rotator cuff tear. Clin Anat 2021; 35:94-102. [PMID: 34668243 PMCID: PMC9298298 DOI: 10.1002/ca.23800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 09/19/2021] [Accepted: 10/11/2021] [Indexed: 11/14/2022]
Abstract
This study aimed to compare the effect of the load of the upper limb on the stiffness of supraspinatus muscle regions during isometric shoulder abduction in the scapular plane in healthy individuals and patients with a rotator cuff tear. Thirteen male patients were scheduled for arthroscopic rotator cuff repair, and 13 healthy male individuals were recruited. The movement task involved 30° isometric shoulder abduction in the scapular plane. The tasks included passive abduction, abduction with half‐weight of the upper limb (1/2‐weight), and full weight of the upper limb (full‐weight). The stiffness of the supraspinatus muscle (anterior superficial, anterior deep, posterior superficial, and posterior deep regions) was recorded using ultrasound shear‐wave elastography. The stiffness of the anterior superficial region on the affected side was significantly lower than that on the control side for the 1/2‐weight and full‐weight tasks. The stiffness of the anterior deep, posterior superficial, and posterior deep regions was not affected. This is the first study that investigated the mechanical effects of different loads on different supraspinatus muscle regions in rotator cuff tear patients. Our results indicate that the anterior superficial region in rotator cuff tear patients was mainly responsible for reduced active stiffness. This might be because this region contributes to force exertion and exhibits atrophy in rotator cuff tears. Hence, the anterior superficial region could be a focal point of quantitative dysfunction evaluation of the supraspinatus muscle in the case of a rotator cuff tear.
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Affiliation(s)
- Yoshinari Sakaki
- Department of Rehabilitation, Hitsujigaoka Hospital, Sapporo, Japan.,Second Division of Physical Therapy, School of Health Sciences, Sapporo Medical University, Sapporo, Japan
| | - Keigo Taniguchi
- Second Division of Physical Therapy, School of Health Sciences, Sapporo Medical University, Sapporo, Japan
| | - Masaki Katayose
- Second Division of Physical Therapy, School of Health Sciences, Sapporo Medical University, Sapporo, Japan
| | - Hideji Kura
- Department of Orthopaedic Surgery, Hitsujigaoka Hospital, Sapporo, Japan
| | - Kenji Okamura
- Department of Orthopaedic Surgery, Hitsujigaoka Hospital, Sapporo, Japan
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15
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Paraspinal Muscle Contractile Function is Impaired in the ENT1-deficient Mouse Model of Progressive Spine Pathology. Spine (Phila Pa 1976) 2021; 46:E710-E718. [PMID: 33332787 DOI: 10.1097/brs.0000000000003882] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Basic science study of the relationship between spine pathology and the contractile ability of the surrounding muscles. OBJECTIVE The aim of this study was to investigate single muscle fiber contractile function in a model of progressive spine mineralization (ENT1-/- mice). SUMMARY OF BACKGROUND DATA Altered muscle structure and function have been associated with various spine pathologies; however, studies to date have provided limited insight into the fundamental ability of spine muscles to actively contract and generate force, and how this may change in response to spine pathology. METHODS Experiments were performed on two groups (ENT1-/- [KO] and ENT1+/+ [WT]) of mice at 8 months of age (n = 12 mice/group). Single muscle fibers were isolated from lumbar multifidus and erector spinae, as well as tibialis anterior (a non-spine-related control) and tested to determine their active contractile characteristics. RESULTS The multifidus demonstrated decreases in specific force (type IIax fibers: 36% decrease; type IIb fibers: 29% decrease), active modulus (type IIax: 35% decrease; type IIb: 30% decrease), and unloaded shortening velocity (Vo) (type IIax: 31% decrease) in the ENT1-/- group when compared to WT controls. The erector spinae specific force was reduced in the ENT1-/- mice when compared to WT (type IIax: 29% decrease), but active modulus and Vo were unchanged. There were no differences in any of the active contractile properties of the lower limb TA muscle, validating that impairments observed in the spine muscles were specific to the underlying spine pathology and not the global loss of ENT1. CONCLUSION These results provide the first direct evidence of cellular level impairments in the active contractile force generating properties of spine muscles in response to chronic spine pathology.Level of Evidence: N/A.
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16
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Silva Andrade B, Siqueira S, de Assis Soares WR, de Souza Rangel F, Santos NO, dos Santos Freitas A, Ribeiro da Silveira P, Tiwari S, Alzahrani KJ, Góes-Neto A, Azevedo V, Ghosh P, Barh D. Long-COVID and Post-COVID Health Complications: An Up-to-Date Review on Clinical Conditions and Their Possible Molecular Mechanisms. Viruses 2021; 13:700. [PMID: 33919537 PMCID: PMC8072585 DOI: 10.3390/v13040700] [Citation(s) in RCA: 229] [Impact Index Per Article: 57.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 04/09/2021] [Accepted: 04/13/2021] [Indexed: 02/06/2023] Open
Abstract
The COVID-19 pandemic has infected millions worldwide, leaving a global burden for long-term care of COVID-19 survivors. It is thus imperative to study post-COVID (i.e., short-term) and long-COVID (i.e., long-term) effects, specifically as local and systemic pathophysiological outcomes of other coronavirus-related diseases (such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS)) were well-cataloged. We conducted a comprehensive review of adverse post-COVID health outcomes and potential long-COVID effects. We observed that such adverse outcomes were not localized. Rather, they affected different human systems, including: (i) immune system (e.g., Guillain-Barré syndrome, rheumatoid arthritis, pediatric inflammatory multisystem syndromes such as Kawasaki disease), (ii) hematological system (vascular hemostasis, blood coagulation), (iii) pulmonary system (respiratory failure, pulmonary thromboembolism, pulmonary embolism, pneumonia, pulmonary vascular damage, pulmonary fibrosis), (iv) cardiovascular system (myocardial hypertrophy, coronary artery atherosclerosis, focal myocardial fibrosis, acute myocardial infarction, cardiac hypertrophy), (v) gastrointestinal, hepatic, and renal systems (diarrhea, nausea/vomiting, abdominal pain, anorexia, acid reflux, gastrointestinal hemorrhage, lack of appetite/constipation), (vi) skeletomuscular system (immune-mediated skin diseases, psoriasis, lupus), (vii) nervous system (loss of taste/smell/hearing, headaches, spasms, convulsions, confusion, visual impairment, nerve pain, dizziness, impaired consciousness, nausea/vomiting, hemiplegia, ataxia, stroke, cerebral hemorrhage), (viii) mental health (stress, depression and anxiety). We additionally hypothesized mechanisms of action by investigating possible molecular mechanisms associated with these disease outcomes/symptoms. Overall, the COVID-19 pathology is still characterized by cytokine storm that results to endothelial inflammation, microvascular thrombosis, and multiple organ failures.
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Affiliation(s)
- Bruno Silva Andrade
- Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia CEP 45206-190, Brazil; (B.S.A.); (S.S.); (W.R.d.A.S.); (F.d.S.R.); (A.d.S.F.); (P.R.d.S.)
| | - Sérgio Siqueira
- Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia CEP 45206-190, Brazil; (B.S.A.); (S.S.); (W.R.d.A.S.); (F.d.S.R.); (A.d.S.F.); (P.R.d.S.)
| | - Wagner Rodrigues de Assis Soares
- Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia CEP 45206-190, Brazil; (B.S.A.); (S.S.); (W.R.d.A.S.); (F.d.S.R.); (A.d.S.F.); (P.R.d.S.)
- Departamento de Saúde II, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia CEP 45206-190, Brazil
| | - Fernanda de Souza Rangel
- Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia CEP 45206-190, Brazil; (B.S.A.); (S.S.); (W.R.d.A.S.); (F.d.S.R.); (A.d.S.F.); (P.R.d.S.)
- Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia CEP 45662-900, Brazil;
| | - Naiane Oliveira Santos
- Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia CEP 45662-900, Brazil;
| | - Andria dos Santos Freitas
- Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia CEP 45206-190, Brazil; (B.S.A.); (S.S.); (W.R.d.A.S.); (F.d.S.R.); (A.d.S.F.); (P.R.d.S.)
- Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil; (S.T.); (V.A.)
| | - Priscila Ribeiro da Silveira
- Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia CEP 45206-190, Brazil; (B.S.A.); (S.S.); (W.R.d.A.S.); (F.d.S.R.); (A.d.S.F.); (P.R.d.S.)
| | - Sandeep Tiwari
- Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil; (S.T.); (V.A.)
| | - Khalid J Alzahrani
- Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;
| | - Aristóteles Góes-Neto
- Laboratório de Biologia Molecular e Computacional de Fungos, Departamento de Microbiologia, Insti-tuto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais CEP 31270-901, Brazil;
| | - Vasco Azevedo
- Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil; (S.T.); (V.A.)
| | - Preetam Ghosh
- Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USA;
| | - Debmalya Barh
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Bio-technology (IIOAB), Nonakuri, Purba Medinipur, West Bengal 721172, India
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17
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Yuan T, Qian H, Yu X, Meng J, Lai CT, Jiang H, Zhao JN, Bao NR. Proteomic analysis reveals rotator cuff injury caused by oxidative stress. Ther Adv Chronic Dis 2021; 12:2040622320987057. [PMID: 33796243 PMCID: PMC7975570 DOI: 10.1177/2040622320987057] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 12/18/2020] [Indexed: 12/16/2022] Open
Abstract
Background and aims: Rotator cuff tendinopathy is common and is related to pain and dysfunction.
However, the pathological mechanism of rotator cuff injury and shoulder pain
is unclear. Objective: to investigate the pathological mechanism of rotator
cuff injury and shoulder pain, and screen out the marker proteins related to
rotator cuff injury by proteomics. Methods: Subacromial synovium specimens were collected from patients undergoing
shoulder arthroscopic surgery. The experimental group were patients with
rotator cuff repair surgery, and the control group were patients with
habitual dislocation of the shoulder joint. Pathological examination was
performed, and then followed by non-labeled quantitative proteomic
detection. Finally, from analysis of the biological information of the
samples, specific proteins related to rotator cuff injury and shoulder pain
were deduced by functional analysis of differential proteins. Results: All the patients in experimental groups were representative. A large number
of adipocytes and inflammatory cells were found in the pathological sections
of the experimental group; the proteomics analysis screen identified 80
proteins with significant differences, and the analysis of protein function
revealed that S100A11 (p = 0.011), PLIN4
(p = 0.017), HYOU1 (p = 0.002) and
CLIC1 (p = 0.007) were closely related to oxidative stress
and chronic inflammation. Conclusion: Rotator cuff injury is closely related to oxidative stress and chronic
inflammatory response, and the results suggest that the expression of
S100A11, PLIN4, HYOU1 and CLIC1 in the synovium of rotator cuff injury
provides a new marker for the study of its pathological mechanism.
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Affiliation(s)
- Tao Yuan
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Hong Qian
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xin Yu
- Department of Orthopedics, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jia Meng
- Department of Orthopedics, Jinling Hospital, Nanjing, China
| | - Cheng-Teng Lai
- Department of Orthopedics, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Hui Jiang
- Department of Orthopedics, Jinling Hospital, Nanjing, China
| | - Jian-Ning Zhao
- Department of Orthopedics, Nanjing Jinling Hospital, 305 Zhongshan East Road, Nanjing 210002, China The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China Department of Orthopedics, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
| | - Ni-Rong Bao
- Department of Orthopedics, Nanjing Jinling Hospital, 305 Zhongshan East Road, Nanjing 210002, China The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China Department of Orthopedics, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
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18
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Van Pelt DW, Kharaz YA, Sarver DC, Eckhardt LR, Dzierzawski JT, Disser NP, Piacentini AN, Comerford E, McDonagh B, Mendias CL. Multiomics analysis of the mdx/mTR mouse model of Duchenne muscular dystrophy. Connect Tissue Res 2021; 62:24-39. [PMID: 32664808 DOI: 10.1080/03008207.2020.1791103] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE/AIM Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease characterized by extensive muscle weakness. Patients with DMD lack a functional dystrophin protein, which transmits force and organizes the cytoskeleton of skeletal muscle. Multiomic studies have been proposed as a way to obtain novel insight about disease processes from preclinical models, and we used this approach to study pathological changes in dystrophic muscles. MATERIALS AND METHODS We evaluated hindlimb muscles of male mdx/mTR mice, which lack a functional dystrophin protein and have deficits in satellite cell abundance and proliferative capacity. Wild type (WT) C57BL/6 J mice served as controls. Muscle fiber contractility was measured, along with changes in the transcriptome using RNA sequencing, and in the proteome, metabolome, and lipidome using mass spectrometry. RESULTS While mdx/mTR mice displayed gross pathological changes and continued cycles of degeneration and regeneration, we found no differences in permeabilized fiber contractility between strains. However, there were numerous changes in the transcriptome and proteome related to protein balance, contractile elements, extracellular matrix, and metabolism. There was only a 53% agreement in fold-change data between the proteome and transcriptome. Numerous changes in markers of skeletal muscle metabolism were observed, with dystrophic muscles exhibiting elevated glycolytic metabolites such as 6-phosphoglycerate, fructose-6-phosphate and glucose-6-phosphate, fructose bisphosphate, phosphorylated hexoses, and phosphoenolpyruvate. CONCLUSIONS These findings highlight the utility of multiomics in studying muscle disease, and provide additional insight into the pathological changes in dystrophic muscles that might help to indirectly guide evidence-based nutritional or exercise prescription in DMD patients.
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Affiliation(s)
- Douglas W Van Pelt
- Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky , Lexington, KY, USA
| | - Yalda A Kharaz
- Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool , Liverpool, UK
| | - Dylan C Sarver
- Department of Orthopaedic Surgery, University of Michigan Medical School , Ann Arbor, MI, USA
| | - Logan R Eckhardt
- Department of Orthopaedic Surgery, University of Michigan Medical School , Ann Arbor, MI, USA
| | - Justin T Dzierzawski
- Department of Orthopaedic Surgery, University of Michigan Medical School , Ann Arbor, MI, USA
| | | | - Alex N Piacentini
- Research Institute, Hospital for Special Surgery , New York, NY, USA
| | - Eithne Comerford
- Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool , Liverpool, UK
| | - Brian McDonagh
- Department of Physiology, School of Medicine, National University of Ireland , Galway, Ireland
| | - Christopher L Mendias
- Department of Orthopaedic Surgery, University of Michigan Medical School , Ann Arbor, MI, USA.,Research Institute, Hospital for Special Surgery , New York, NY, USA.,Department of Physiology & Biophysics, Weill Cornell Medical College , New York, NY, USA
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19
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Disser NP, De Micheli AJ, Schonk MM, Konnaris MA, Piacentini AN, Edon DL, Toresdahl BG, Rodeo SA, Casey EK, Mendias CL. Musculoskeletal Consequences of COVID-19. J Bone Joint Surg Am 2020; 102:1197-1204. [PMID: 32675661 PMCID: PMC7508274 DOI: 10.2106/jbjs.20.00847] [Citation(s) in RCA: 252] [Impact Index Per Article: 50.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is an emerging pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients who become infected with SARS-CoV-2 are asymptomatic or have mild symptoms, some patients develop severe symptoms that can permanently detract from their quality of life. SARS-CoV-2 is closely related to SARS-CoV-1, which causes severe acute respiratory syndrome (SARS). Both viruses infect the respiratory system, and there are direct and indirect effects of this infection on multiple organ systems, including the musculoskeletal system. Epidemiological data from the SARS pandemic of 2002 to 2004 identified myalgias, muscle dysfunction, osteoporosis, and osteonecrosis as common sequelae in patients with moderate and severe forms of this disease. Early studies have indicated that there is also considerable musculoskeletal dysfunction in some patients with COVID-19, although long-term follow-up studies have not yet been conducted. The purpose of this article was to summarize the known musculoskeletal pathologies in patients with SARS or COVID-19 and to combine this with computational modeling and biochemical signaling studies to predict musculoskeletal cellular targets and long-term consequences of the SARS-CoV-2 infection.
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Affiliation(s)
| | - Andrea J. De Micheli
- Hospital for Special Surgery, New York, NY
- Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY
| | | | | | | | | | | | | | | | - Christopher L. Mendias
- Hospital for Special Surgery, New York, NY
- Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY
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20
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Kuwahara Y, Kishimoto KN, Itoigawa Y, Okuno H, Hatta T, Matsuzawa G, Itoi E. Fatty degeneration and wnt10b expression in the supraspinatus muscle after surgical repair of torn rotator cuff tendon. J Orthop Surg (Hong Kong) 2020; 27:2309499019864817. [PMID: 31382826 DOI: 10.1177/2309499019864817] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
PURPOSE In the torn rotator cuff muscles, decreased expression of wnt10b prior to elevation of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) has previously been reported. The purpose of this study is to elucidate the expression profiles of these adipogenesis-related genes after rotator cuff detachment and reattachment in a rabbit model. METHODS We investigated gene expression profiles of PPARγ, C/EBPα, and wnt10b in different parts of rabbit supraspinatus (SSP) muscle after tendon detachment (n = 6 for each time point). In addition, we assessed expression of the same genes after SSP reattachment with different intervals from initial detachment (n = 6). Fatty degeneration of the SSP muscle was examined by Oil red-O staining. Gene expression profiles were examined by quantitative real-time polymerase chain reaction. RESULTS After SSP detachment, Oil red-O-positive oil deposits increased after 3 weeks. In the SSP reattachment model, numerous Oil red-O-positive cells were present at 5-week reattachment, following 2- and 3-week detachment. PPARγ and C/EBPα messenger ribonucleic acid expression exhibited a significant increase at 2 and 3 weeks after SSP detachment and remained increased at 5-week reattachment after 2- and 3-week detachment. A decreased expression of wnt10b was observed from 1 week after SSP detachment. Expression of wnt10b was recovered not in the central area of the SSP muscle but in the periphery after reattachment. Adipogenic change was not observed when SSP tendon was reattached after 1-week detachment. CONCLUSIONS These results may suggest that once the adipogenic transcription factors, PPARγ and C/EBPα, were elevated, repair surgery after rotator cuff tear could not prevent the emergence of fat in the SSP muscle.
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Affiliation(s)
- Yoshiyuki Kuwahara
- 1 Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan
| | - Koshi N Kishimoto
- 1 Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan.,2 Department of Orthopaedic Surgery, Tohoku Kosai Hospital, Sendai, Japan
| | - Yoshiaki Itoigawa
- 3 Department of Orthopaedic Surgery, Juntendo University, Tokyo, Japan
| | - Hiroshi Okuno
- 1 Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan
| | - Taku Hatta
- 1 Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan
| | - Gaku Matsuzawa
- 1 Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan
| | - Eiji Itoi
- 1 Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan
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21
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Kunz P, Mick P, Gross S, Schmidmaier G, Zeifang F, Weber MA, Fischer C. Contrast-Enhanced Ultrasound (CEUS) as Predictor for Early Retear and Functional Outcome After Supraspinatus Tendon Repair. J Orthop Res 2020; 38:1150-1158. [PMID: 31769543 DOI: 10.1002/jor.24535] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 11/19/2019] [Indexed: 02/04/2023]
Abstract
Supraspinatus (SSP) tendon tears represent a common indication for shoulder surgery. Yet, prediction of postoperative function and tendon retear remains challenging and primarily relies on morphologic magnetic resonance imaging (MRI)-based parameters, supported by patients' demographic data like age, gender, and comorbidities. Considering continuously high retear rates, especially in patients with larger tears and negative prognostic factors, improved outcome prediction could be of high clinical value. Contrast-enhanced ultrasound (CEUS) enables an assessment of dynamic perfusion of the SSP muscle. As a potential surrogate for muscle vitality, CEUS might reflect functional properties of the SSP and support improved outcome prediction after tendon repair. Fifty patients with isolated SSP tendon tears were prospectively enrolled. Preoperatively, SSP muscle perfusion was quantified by CEUS and conventional morphologic parameters like tear size, fatty infiltration, and tendon retraction were assessed by MRI. At six months follow-up, shoulder function, tendon integrity, and muscle perfusion were reassessed. The predictive value of preoperative CEUS for postoperative shoulder function and tendon integrity was evaluated. 35 patients entered the statistical analysis. Preoperative CEUS-based assessment of SSP perfusion significantly correlated with early postoperative shoulder function (Constant, r = 0.48, p < 0.018) and tendon retear (r = 0.67, p < 0.001). CEUS-based subgroup analysis identified patients with exceptionally high, respectively low risk for tendon retear. CEUS-based assessment of the SSP seemed to predict early shoulder function and tendon retear after SSP repair and allowed to identify patient subgroups with exceptionally high or low risk for tendon retear. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:1150-1158, 2020.
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Affiliation(s)
- Pierre Kunz
- Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Ultrasound Center, HTRG-Heidelberg Trauma Research Group, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118, Heidelberg, Germany.,Clinic for Shoulder and Elbow Surgery, Catholic Hospital Mainz, An der Goldgrube 11, 55131, Mainz, Germany
| | - Paul Mick
- Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Ultrasound Center, HTRG-Heidelberg Trauma Research Group, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118, Heidelberg, Germany
| | - Sascha Gross
- Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Ultrasound Center, HTRG-Heidelberg Trauma Research Group, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118, Heidelberg, Germany
| | - Gerhard Schmidmaier
- Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Ultrasound Center, HTRG-Heidelberg Trauma Research Group, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118, Heidelberg, Germany
| | - Felix Zeifang
- Ethianum Klinik Heidelberg, Voßstraße 6, 69115, Heidelberg, Germany
| | - Marc-André Weber
- Institute of Diagnostic and Interventional Radiology, University Medical Center Rostock, Ernst-Heydemann-Straße 6, 18057, Rostock, Germany
| | - Christian Fischer
- Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Ultrasound Center, HTRG-Heidelberg Trauma Research Group, Heidelberg University Hospital, Schlierbacher Landstraße 200a, 69118, Heidelberg, Germany
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22
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Talarek JR, Piacentini AN, Konja AC, Wada S, Swanson JB, Nussenzweig SC, Dines JS, Rodeo SA, Mendias CL. The MRL/MpJ Mouse Strain Is Not Protected From Muscle Atrophy and Weakness After Rotator Cuff Tear. J Orthop Res 2020; 38:811-822. [PMID: 31696955 PMCID: PMC7071998 DOI: 10.1002/jor.24516] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2019] [Accepted: 11/04/2019] [Indexed: 02/04/2023]
Abstract
Chronic rotator cuff tears are a common source of shoulder pain and disability. Patients with rotator cuff tears often have substantial weakness, fibrosis, and fat accumulation, which limit successful surgical repair and postoperative rehabilitation. The Murphy Roths Large (MRL) strain of mice have demonstrated superior healing and protection against pathological changes in several disease and injury conditions. We tested the hypothesis that, compared with the commonly used C57Bl/6 (B6) strain, MRL mice would have less muscle fiber atrophy and fat accumulation, and be protected against the loss in force production that occurs after cuff tear. Adult male B6 and MRL mice were subjected to a rotator cuff tear, and changes in muscle fiber contractility and histology were measured. RNA sequencing and shotgun metabolomics and lipidomics were also performed. The muscles were harvested one month after tear. B6 and MRL mice had a 40% reduction in relative muscle force production after rotator cuff tear. RNA sequencing identified an increase in fibrosis-associated genes and a reduction in mitochondrial metabolism genes. The markers of glycolytic metabolism increased in B6 mice, while MRL mice appeared to increase amino acid metabolism after tear. There was an accumulation of lipid after injury, although there was a divergent response between B6 and MRL mice in the types of lipid species that accrued. There were strain-specific differences between the transcriptome, metabolome, and lipidome of B6 and MRL mice, but these differences did not protect MRL mice from weakness and pathological changes after rotator cuff tear. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:811-822, 2020.
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Affiliation(s)
| | | | | | | | | | | | - Joshua S Dines
- Hospital for Special Surgery, New York, NY
- Department of Orthopaedic Surgery, Weill Cornell Medical College, New York, NY
| | - Scott A Rodeo
- Hospital for Special Surgery, New York, NY
- Department of Orthopaedic Surgery, Weill Cornell Medical College, New York, NY
| | - Christopher L Mendias
- Hospital for Special Surgery, New York, NY
- Department of Orthopaedic Surgery, Weill Cornell Medical College, New York, NY
- Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY
- Corresponding Author: Christopher Mendias, PhD, Hospital for Special Surgery, 535 E 70th St, New York, NY 10021, USA, +1 212-606-1785 office, +1 212-249-2373 fax,
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23
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Yoo SJ, Lee S, Song Y, Kim CK, Lee BG, Bae J. Elasticity of torn supraspinatus tendons measured by shear wave elastography: a potential surrogate marker of chronicity? Ultrasonography 2020; 39:144-151. [PMID: 32106664 PMCID: PMC7065989 DOI: 10.14366/usg.19035] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 01/02/2020] [Indexed: 11/03/2022] Open
Abstract
PURPOSE This study investigated whether shear wave elastography (SWE) could be used to estimate the chronicity of supraspinatus tendon (SST) tears. METHODS A retrospective study was performed. From November 2015 to July 2016, 113 patients (52 men, 61 women; age range, 21 to 79 years) with persistent shoulder pain underwent 119 rotator cuff tendon examinations by routine B-mode ultrasonography, while SST elasticity was measured using SWE. Following the exclusion of eight suboptimal examinations, four examinations with missing SST measurements, and 27 examinations of patients with other conditions, 80 examinations were analyzed. A torn SST was found in 54 examinations (27 with a partial-thickness tear and 27 with a full-thickness tear). Elasticity values were compared in multiple ways. The results were analyzed using the Mann-Whitney U test or Kruskal-Wallis test. RESULTS No statistically significant difference in elasticity values (in kPa) was found between normal (median, 94.65; interquartile range [IQR], 87.43 to 105.47) and torn SSTs (median, 96.79; IQR, 86.71 to 108.56) or between full-thickness tears (median, 93.80; IQR, 82.50 to 108.33) and partial-thickness tears (median, 96.83; IQR, 90.60 to 112.20). However, there was a statistically significant difference in elasticity according to whether the duration of symptoms was 1 year or less (median, 92.20; IQR, 84.01 to 104.38) or longer than 1 year (median, 105.10; IQR, 100.41 to 116.03; P=0.032). CONCLUSION Elasticity values were significantly higher in torn SSTs in patients with chronic shoulder pain that had persisted for more than 1 year. Further studies with larger samples seem warranted to determine whether elasticity values measured by SWE can be used preoperatively as a surrogate marker of the chronicity of a rotator cuff tendon tear.
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Affiliation(s)
- Seung-Jin Yoo
- Department of Radiology, Hanyang University College of Medicine, Seoul, Korea
| | - Seunghun Lee
- Department of Radiology, Hanyang University College of Medicine, Seoul, Korea
| | - Yoonah Song
- Department of Radiology, Hanyang University College of Medicine, Seoul, Korea
| | - Chun Ki Kim
- Department of Nuclear Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Bong Gun Lee
- Department of Orthopedic Surgery, Hanyang University College of Medicine, Seoul, Korea
| | - Jiyoon Bae
- Department of Pathology, National Police Hospital, Seoul, Korea
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24
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Wang C, Song W, Chen B, Liu X, He Y. Exosomes Isolated From Adipose-Derived Stem Cells: A New Cell-Free Approach to Prevent the Muscle Degeneration Associated With Torn Rotator Cuffs. Am J Sports Med 2019; 47:3247-3255. [PMID: 31560856 DOI: 10.1177/0363546519876323] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Fatty infiltration, inflammation, and apoptosis are common degenerative changes in patients with chronic rotator cuff tears that can lead to muscle atrophy and can even result in massive irreparable rotator cuff tears. Some data have demonstrated the proregenerative, anti-inflammatory, and anti-apoptotic properties of stem cell-derived exosomes in some orthopaedic disorders, but their effect on torn rotator cuff muscles has never been investigated. PURPOSE To study the effect of exosomes isolated from human adipose-derived stem cells (ASCs-Exos) on muscle degeneration, regeneration, and biomechanical properties in a rat model of a massive rotator cuff tear (MRCT). STUDY DESIGN Controlled laboratory study. METHODS A bilateral supraspinatus and infraspinatus tenotomy was performed on rats to create an MRCT model. Forty-two rats were randomly assigned to 3 groups: the sham surgery group, the saline group (lesions treated with a saline injection), and the ASCs-Exos group (lesions treated with an ASCs-Exos injection). Wet muscle weight, fatty infiltration, inflammation, vascularization, regeneration, and biomechanical properties were evaluated at 8 and 16 weeks after surgery. RESULTS The results revealed that the ASCs-Exos treatment could prevent the atrophy, fatty infiltration, inflammation, and vascularization of muscles in the MRCT model (P < .001). Additionally, the myofiber regeneration and biomechanical properties of ASCs-Exos-treated rotator cuffs were significantly elevated compared with those in the saline-treated group (P < .001). CONCLUSION This study demonstrates that ASCs-Exos can effectively decrease atrophy and degeneration and improve muscle regeneration and biomechanical properties in torn rotator cuff muscles. CLINICAL RELEVANCE ASCs-Exos can be used as a new cell-free approach to prevent the muscle degeneration associated with torn rotator cuffs and may be helpful to repair torn rotator cuffs. Nevertheless, further work needs to be done in a large animal model owing to the inherent regenerative potential possessed by rodents.
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Affiliation(s)
- Chongyang Wang
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Wei Song
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Bi Chen
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Xudong Liu
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Yaohua He
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.,Department of Orthopedics, Shanghai Sixth People's Hospital, Jinshan Branch, Shanghai, China
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25
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Sarver DC, Sugg KB, Talarek JR, Swanson JB, Oliver DJ, Hinken AC, Kramer HF, Mendias CL. Prostaglandin D 2 signaling is not involved in the recovery of rat hind limb tendons from injury. Physiol Rep 2019; 7:e14289. [PMID: 31782241 PMCID: PMC6882956 DOI: 10.14814/phy2.14289] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 10/24/2019] [Accepted: 10/25/2019] [Indexed: 12/19/2022] Open
Abstract
Injured tendons heal through the formation of a fibrovascular scar that has inferior mechanical properties compared to native tendon tissue. Reducing inflammation that occurs as a result of the injury could limit scar formation and improve functional recovery of tendons. Prostaglandin D2 (PGD2 ) plays an important role in promoting inflammation in some injury responses and chronic disease processes, and the inhibition of PGD2 has improved healing and reduced disease burden in animal models and early clinical trials. Based on these findings, we sought to determine the role of PGD2 signaling in the healing of injured tendon tissue. We tested the hypothesis that a potent and specific inhibitor of hematopoietic PGD synthase (HPGDS), GSK2894631A, would improve the recovery of tendons of adult male rats following an acute tenotomy and repair. To test this hypothesis, we performed a full-thickness plantaris tendon tenotomy followed by immediate repair and treated rats twice daily with either 0, 2, or 6 mg/kg of GSK2894631A. Tendons were collected either 7 or 21 days after surgical repair, and mechanical properties of tendons were assessed along with RNA sequencing and histology. While there were some differences in gene expression across groups, the targeted inhibition of HPGDS did not impact the functional repair of tendons after injury, as HPGDS expression was surprisingly low in injured tendons. These results indicate that PGD2 signaling does not appear to be important in modulating the repair of injured tendon tissue.
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Affiliation(s)
- Dylan C. Sarver
- Department of Orthopaedic SurgerySection of Plastic & Reconstructive SurgeryUniversity of Michigan Medical SchoolAnn ArborMIUSA
- Present address:
Department of PhysiologyJohns Hopkins University School of MedicineBaltimoreMDUSA
| | - Kristoffer B. Sugg
- Department of Orthopaedic SurgerySection of Plastic & Reconstructive SurgeryUniversity of Michigan Medical SchoolAnn ArborMIUSA
- Department of Molecular & Integrative PhysiologySection of Plastic & Reconstructive SurgeryUniversity of Michigan Medical SchoolAnn ArborMIUSA
- Department of SurgerySection of Plastic & Reconstructive SurgeryUniversity of Michigan Medical SchoolAnn ArborMIUSA
| | - Jeffrey R. Talarek
- Department of Orthopaedic SurgerySection of Plastic & Reconstructive SurgeryUniversity of Michigan Medical SchoolAnn ArborMIUSA
- Department of Molecular & Integrative PhysiologySection of Plastic & Reconstructive SurgeryUniversity of Michigan Medical SchoolAnn ArborMIUSA
- Hospital for Special SurgeryNew YorkNYUSA
| | | | | | - Aaron C. Hinken
- Muscle Metabolism DPUGlaxoSmithKline PharmaceuticalsKing of PrussiaPAUSA
| | - Henning F. Kramer
- Muscle Metabolism DPUGlaxoSmithKline PharmaceuticalsKing of PrussiaPAUSA
| | - Christopher L. Mendias
- Department of Orthopaedic SurgerySection of Plastic & Reconstructive SurgeryUniversity of Michigan Medical SchoolAnn ArborMIUSA
- Department of Molecular & Integrative PhysiologySection of Plastic & Reconstructive SurgeryUniversity of Michigan Medical SchoolAnn ArborMIUSA
- Hospital for Special SurgeryNew YorkNYUSA
- Department of Physiology & BiophysicsWeill Cornell Medical CollegeNew YorkNYUSA
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26
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Qazi TH, Duda GN, Ort MJ, Perka C, Geissler S, Winkler T. Cell therapy to improve regeneration of skeletal muscle injuries. J Cachexia Sarcopenia Muscle 2019; 10:501-516. [PMID: 30843380 PMCID: PMC6596399 DOI: 10.1002/jcsm.12416] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 01/27/2019] [Indexed: 12/14/2022] Open
Abstract
Diseases that jeopardize the musculoskeletal system and cause chronic impairment are prevalent throughout the Western world. In Germany alone, ~1.8 million patients suffer from these diseases annually, and medical expenses have been reported to reach 34.2bn Euros. Although musculoskeletal disorders are seldom fatal, they compromise quality of life and diminish functional capacity. For example, musculoskeletal disorders incur an annual loss of over 0.8 million workforce years to the German economy. Among these diseases, traumatic skeletal muscle injuries are especially problematic because they can occur owing to a variety of causes and are very challenging to treat. In contrast to chronic muscle diseases such as dystrophy, sarcopenia, or cachexia, traumatic muscle injuries inflict damage to localized muscle groups. Although minor muscle trauma heals without severe consequences, no reliable clinical strategy exists to prevent excessive fibrosis or fatty degeneration, both of which occur after severe traumatic injury and contribute to muscle degeneration and dysfunction. Of the many proposed strategies, cell-based approaches have shown the most promising results in numerous pre-clinical studies and have demonstrated success in the handful of clinical trials performed so far. A number of myogenic and non-myogenic cell types benefit muscle healing, either by directly participating in new tissue formation or by stimulating the endogenous processes of muscle repair. These cell types operate via distinct modes of action, and they demonstrate varying levels of feasibility for muscle regeneration depending, to an extent, on the muscle injury model used. While in some models the injury naturally resolves over time, other models have been developed to recapitulate the peculiarities of real-life injuries and therefore mimic the structural and functional impairment observed in humans. Existing limitations of cell therapy approaches include issues related to autologous harvesting, expansion and sorting protocols, optimal dosage, and viability after transplantation. Several clinical trials have been performed to treat skeletal muscle injuries using myogenic progenitor cells or multipotent stromal cells, with promising outcomes. Recent improvements in our understanding of cell behaviour and the mechanistic basis for their modes of action have led to a new paradigm in cell therapies where physical, chemical, and signalling cues presented through biomaterials can instruct cells and enhance their regenerative capacity. Altogether, these studies and experiences provide a positive outlook on future opportunities towards innovative cell-based solutions for treating traumatic muscle injuries-a so far unmet clinical need.
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Affiliation(s)
- Taimoor H Qazi
- Julius Wolff Institute, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Georg N Duda
- Julius Wolff Institute, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Berlin-Brandenburg School for Regenerative Therapies, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Melanie J Ort
- Julius Wolff Institute, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Berlin-Brandenburg School for Regenerative Therapies, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Carsten Perka
- Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Sven Geissler
- Julius Wolff Institute, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Tobias Winkler
- Julius Wolff Institute, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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27
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Histological Evidence of Intrinsic Muscle Degeneration in Compression Ulnar Neuropathy. Ann Plast Surg 2019; 82:541-545. [PMID: 30950876 DOI: 10.1097/sap.0000000000001853] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE We investigated the histological characteristics of the tissues in the intrinsic hand muscles of patients with compressive ulnar neuropathy (CUN) to determine how the compromised nerve influences the target muscle. METHODS In total, 83 patients underwent surgery for CUN in our institution between March 2015 and August 2017. Of these, 45 patients who met our inclusion/exclusion criteria were initially included in this study. Basic demographic data including age, sex, hand dominance, duration of symptoms, bone mineral density, and clinical stage were evaluated. During the ulnar nerve decompression surgery, a biopsy of the ipsilateral adductor pollicis was performed. Using the biopsy samples, we analyzed the tissue composition and degree of degeneration, and investigated the association with demographic factors and clinical status. RESULTS The ratio of muscle/connective tissue/fat was 62.62 ± 8.27%/23.44 ± 4.10%/14.16 ± 6.68% in the affected muscle. The ratio was different than that of samples taken from control groups. In samples containing muscle fibers, although the total fat content remained low, fat was consistently concentrated at the fascicular borders, between fascicles (perifascicular fat, 62.3 ± 18.2% of fascicles), and within fascicles (intrafascicular fat, 35.6 ± 11.8% of fascicles). The proportion of centrally nucleated muscle fibers was also significantly elevated (5.58 ± 4.25%; P < 0.001) compared with that of both controls (1.09 ± 1.26%) and the clinical threshold for abnormal central nuclei (3%). Preoperative scores assessed using Gabel and Amadio criteria were positively correlated with the muscle composition (r = 0.89, P < 0.001). In addition, the clinical status was negatively correlated with the degree of fat accumulation and the proportion of centrally nucleated muscle fibers (r = -0.94, P < 0.001, r = -0.82, P < 0.001). CONCLUSIONS We demonstrated that target muscle in CUN underwent degeneration, which was potentially exacerbated by inflammation, and that the degree of degeneration was correlated with the patient's clinical status. Histologically, reversible recovery of the hand muscles may be possible if decompression of the ulnar nerve is performed at earlier stages.
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Gumucio JP, Qasawa AH, Ferrara PJ, Malik AN, Funai K, McDonagh B, Mendias CL. Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis. FASEB J 2019; 33:7863-7881. [PMID: 30939247 DOI: 10.1096/fj.201802457rr] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Myosteatosis is the pathologic accumulation of lipid that can occur in conjunction with atrophy and fibrosis following skeletal muscle injury. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many clinical studies have demonstrated that the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our objective was to determine the pathologic changes that result in lipid accumulation in injured muscle fibers. We used a rat model of rotator cuff injury in this study because the rotator cuff muscle group is particularly prone to the development of myosteatosis after injury. Muscles were collected from uninjured controls or 10, 30, or 60 d after injury and analyzed using a combination of muscle fiber contractility assessments, RNA sequencing, and undirected metabolomics, lipidomics, and proteomics, along with bioinformatics techniques to identify potential pathways and cellular processes that are dysregulated after rotator cuff tear. Bioinformatics analyses indicated that mitochondrial function was likely disrupted after injury. Based on these findings and given the role that mitochondria play in lipid metabolism, we then performed targeted biochemical and imaging studies and determined that mitochondrial dysfunction and reduced fatty acid oxidation likely leads to the accumulation of lipid in myosteatosis.-Gumucio, J. P., Qasawa, A. H., Ferrara, P. J., Malik, A. N., Funai, K., McDonagh, B., Mendias, C. L. Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis.
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Affiliation(s)
- Jonathan P Gumucio
- Department of Orthopedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.,Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA
| | - Austin H Qasawa
- Department of Orthopedic Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Patrick J Ferrara
- Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, Utah, USA
| | - Afshan N Malik
- Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
| | - Katsuhiko Funai
- Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, Utah, USA
| | - Brian McDonagh
- Department of Physiology, School of Medicine, National University of Ireland, Galway, Ireland
| | - Christopher L Mendias
- Department of Orthopedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.,Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.,Hospital for Special Surgery, New York, New York, USA.,Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York, USA
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Schubert MF, Noah AC, Bedi A, Gumucio JP, Mendias CL. Reduced Myogenic and Increased Adipogenic Differentiation Capacity of Rotator Cuff Muscle Stem Cells. J Bone Joint Surg Am 2019; 101:228-238. [PMID: 30730482 PMCID: PMC6791507 DOI: 10.2106/jbjs.18.00509] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Fat accumulation commonly occurs in chronically torn rotator cuff muscles, and increased fat within the rotator cuff is correlated with poor clinical outcomes. The extent of lipid deposition is particularly pronounced in injured rotator cuff muscles compared with other commonly injured muscles such as the gastrocnemius. Satellite cells, which are a tissue-resident muscle stem-cell population, can differentiate into fat cells. We hypothesized that satellite cells from the rotator cuff have greater intrinsic adipogenic differentiation potential than do gastrocnemius satellite cells, and this difference is due to variations in epigenetic imprinting between the cells. METHODS Satellite cells from gastrocnemius and rotator cuff muscles of mice were cultured in adipogenic media, and the capacity to differentiate into mature muscle cells and adipogenic cells was assessed (n ≥ 9 plates per muscle group). We also performed DNA methylation analysis of gastrocnemius and rotator cuff satellite cells to determine whether epigenetic differences were present between the 2 groups (n = 5 mice per group). RESULTS Compared with the gastrocnemius, satellite cells from the rotator cuff had a 23% reduction in myogenic differentiation and an 87% decrease in the expression of the differentiated muscle cell marker MRF4 (myogenic regulatory factor 4). With respect to adipogenesis, rotator cuff satellite cells had a 4.3-fold increase in adipogenesis, a 12-fold increase in the adipogenic transcription factor PPARγ (peroxisome proliferator-activated receptor gamma), and a 65-fold increase in the adipogenic marker FABP4 (fatty-acid binding protein 4). Epigenetic analysis identified 355 differentially methylated regions of DNA between rotator cuff and gastrocnemius satellite cells, and pathway enrichment analysis suggested that these regions were involved with lipid metabolism and adipogenesis. CONCLUSIONS Satellite cells from rotator cuff muscles have reduced myogenic and increased adipogenic differentiation potential compared with gastrocnemius muscles. There appears to be a cellular and genetic basis behind the generally poor rates of rotator cuff muscle healing. CLINICAL RELEVANCE The reduced myogenic and increased adipogenic capacity of rotator cuff satellite cells is consistent with the increased fat content and poor muscle healing rates often observed for chronically torn rotator cuff muscles. For patients undergoing rotator cuff repair, transplantation of autologous satellite cells from other muscles less prone to fatty infiltration may improve clinical outcomes.
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Affiliation(s)
- Manuel F. Schubert
- Departments of Orthopaedic Surgery (M.F.S., A.C.N., A.B, J.P.G, and C.L.M.) and Molecular and Integrative Physiology (A.C.N, J.P.G., and C.L.M.), University of Michigan Medical School, Ann Arbor, Michigan
| | - Andrew C. Noah
- Departments of Orthopaedic Surgery (M.F.S., A.C.N., A.B, J.P.G, and C.L.M.) and Molecular and Integrative Physiology (A.C.N, J.P.G., and C.L.M.), University of Michigan Medical School, Ann Arbor, Michigan
| | - Asheesh Bedi
- Departments of Orthopaedic Surgery (M.F.S., A.C.N., A.B, J.P.G, and C.L.M.) and Molecular and Integrative Physiology (A.C.N, J.P.G., and C.L.M.), University of Michigan Medical School, Ann Arbor, Michigan
| | - Jonathan P. Gumucio
- Departments of Orthopaedic Surgery (M.F.S., A.C.N., A.B, J.P.G, and C.L.M.) and Molecular and Integrative Physiology (A.C.N, J.P.G., and C.L.M.), University of Michigan Medical School, Ann Arbor, Michigan
| | - Christopher L. Mendias
- Departments of Orthopaedic Surgery (M.F.S., A.C.N., A.B, J.P.G, and C.L.M.) and Molecular and Integrative Physiology (A.C.N, J.P.G., and C.L.M.), University of Michigan Medical School, Ann Arbor, Michigan,Hospital for Special Surgery, New York, NY,Departments of Physiology and Biophysics and Orthopaedic Surgery, Weill Cornell Medical College, New York, NY
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Fischer C, Gross S, Zeifang F, Schmidmaier G, Weber MA, Kunz P. Contrast-Enhanced Ultrasound Determines Supraspinatus Muscle Atrophy After Cuff Repair and Correlates to Functional Shoulder Outcome. Am J Sports Med 2018; 46:2735-2742. [PMID: 30080421 DOI: 10.1177/0363546518787266] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Muscle degeneration as a consequence of rotator cuff tears is mainly assessed by magnetic resonance imaging. Contrast-enhanced ultrasound (CEUS) is a new functional imaging method to assess microvascular perfusion as a fundamental parameter of muscle tissue vitality. In this cross-sectional study, the authors evaluated supraspinatus muscle perfusion after cuff repair and analyzed its association with functional shoulder outcome and the grade of echogenicity in B-mode ultrasound indicating fatty infiltration. HYPOTHESIS The authors expected reduced microperfusion of the operated versus the contralateral supraspinatus muscle and a correlation of the muscular microperfusion with functional shoulder outcome. STUDY DESIGN Cross-sectional study; Level of evidence, 3. METHODS Patients who received unilateral repair of the supraspinatus tendon between 2009 and 2014 were invited for a single follow-up examination. Functional scores were assessed, including the Constant-Murley score and American Shoulder and Elbow Surgeons score. CEUS examination was performed bilaterally in an oblique sagittal plane of the supraspinatus fossa. Perfusion was quantified by the parameters wash-in perfusion index (WiPI) and peak enhancement via VueBox quantification software. The results of the Constant-Murley score, American Shoulder and Elbow Surgeons score, and perfusion parameters were referenced to the contralateral shoulder. Echogenicity of the supraspinatus muscle was classified with a 3-point scale as compared with the trapezius muscle. RESULTS Sixty-seven patients were available, with a mean follow-up of 38.0 ± 18.5 months. Functional assessment showed impaired shoulder function on the operated shoulder as compared with the contralateral side (relative Constant Score [CS], 80% ± 19%). CEUS revealed diminished perfusion on the operated shoulder (WiPI, 55.1% ± 40.2%, P < .001). A strong correlation could be demonstrated between the perfusion deficit and functional impairment (relative WiPI and CS: rs = .644, P < .001). Higher grade of echogenicity in B-mode ultrasound was associated with reduced perfusion. CONCLUSION CEUS could visualize impaired supraspinatus muscle perfusion after rotator cuff repair as compared with the contralateral, healthy shoulder. With its ability to quantify microvascular perfusion as a surrogate parameter for muscle vitality and function, CEUS may serve as a quantitative method to evaluate rotator cuff muscles.
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Affiliation(s)
- Christian Fischer
- Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, HTRG-Heidelberg Trauma Research Group, Heidelberg University Hospital, Heidelberg, Germany
| | - Sascha Gross
- Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, HTRG-Heidelberg Trauma Research Group, Heidelberg University Hospital, Heidelberg, Germany
| | - Felix Zeifang
- Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, HTRG-Heidelberg Trauma Research Group, Heidelberg University Hospital, Heidelberg, Germany
| | - Gerhard Schmidmaier
- Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, HTRG-Heidelberg Trauma Research Group, Heidelberg University Hospital, Heidelberg, Germany
| | - Marc-André Weber
- Institute of Diagnostic and Interventional Radiology, University Medical Center Rostock, Rostock, Germany
| | - Pierre Kunz
- Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, HTRG-Heidelberg Trauma Research Group, Heidelberg University Hospital, Heidelberg, Germany.,Shoulder and Elbow Surgery, Catholic Hospital Mainz, Mainz, Germany
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Gwark JY, Sung CM, Na JB, Park HB. Outcomes of Arthroscopic Rotator Cuff Repair in Patients Who Are 70 Years of Age or Older Versus Under 70 Years of Age: A Sex- and Tear Size-Matched Case-Control Study. Arthroscopy 2018; 34:2045-2053. [PMID: 29789245 DOI: 10.1016/j.arthro.2018.02.047] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 02/21/2018] [Accepted: 02/21/2018] [Indexed: 02/02/2023]
Abstract
PURPOSE To compare the structural and clinical outcomes after arthroscopic rotator cuff repair (ARCR) of a case group aged 70 and above with those of a control group younger than 70, with the 2 groups matched for sex and tear size. METHODS The case group, comprising 53 patients 70 or older, and the control group, comprising 159 patients younger than 70, all received ARCR to 1 shoulder with symptomatic full-thickness rotator cuff tear. The case and the control subjects, who were matched for sex and tear size to minimize bias related to tendon healing, received ARCR during the same period. The mean age was 71.8 ± 2.6 years in the case group and 59.3 ± 7.1 years in the control group. The minimum follow-up period was 1 year in both groups. Cuff integrity was evaluated using ultrasonography. Structural and clinical outcomes of the 2 groups were compared. RESULTS Regarding structural outcomes, the complete healing, partial-thickness retear, and full-thickness retear rates were 66% (35/53), 15% (8/53), and 19% (10/53) in the case group, and 68% (108/159), 19% (30/159), and 13% (21/159), respectively, in the control group. The 2 groups had no significantly different retear rates (P = .52). Regarding clinical outcomes, the mean improvements in range of motion, pain, muscle strength, and age- and sex-matched Constant scores were not significantly different between the 2 groups (P > .37). The preoperative tear size was significantly associated with retear in both studied groups (P = .02). CONCLUSIONS The clinical and structural outcomes of ARCR in patients 70 or older with symptomatic full-thickness rotator cuff tear are comparable with those in patients younger than 70 with at least 1-year follow-up. Preoperative tear size, a biological factor, is a strong predictor for retear. LEVEL OF EVIDENCE Level III, a retrospective comparative (case-control) study.
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Affiliation(s)
- Ji-Yong Gwark
- Department of Orthopaedic Surgery, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Chang-Meen Sung
- Department of Orthopaedic Surgery, Suncheon Hankook Hospital, Suncheon, Republic of Korea
| | - Jae-Boem Na
- Department of Radiology, School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Hyung Bin Park
- Department of Orthopaedic Surgery, School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea.
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Tellier L, Krieger J, Brimeyer A, Coogan A, Falis A, Rinker T, Schudel A, Thomas S, Jarrett C, Willett N, Botchwey E, Temenoff J. Localized SDF-1α Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2018; 4:92-103. [PMID: 30288396 PMCID: PMC6166879 DOI: 10.1007/s40883-018-0052-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 03/31/2018] [Indexed: 10/17/2022]
Abstract
To examine how the chemotactic agent stromal cell-derived factor-1alpha (SDF-1α) modulates the unique cellular milieu within rotator cuff muscle following tendon injury, we developed an injectable, heparin-based microparticle platform to locally present SDF-1α within the supraspinatus muscle following severe rotator cuff injury. SDF-1α loaded, degradable, N-desulfated heparin-based microparticles were fabricated, injected into a rat model of severe rotator cuff injury, and were retained for up to 7 days at the site. The resultant inflammatory cell and mesenchymal stem cell populations were analyzed compared to uninjured contralateral controls and, after 7 days, the fold-change in anti-inflammatory, M2-like macrophages (CD11b+CD68+CD163+, 4.3X fold-change) and mesenchymal stem cells (CD29+CD44+CD90+, 3.0X, respectively) was significantly greater in muscles treated with SDF-1α loaded microparticles than unloaded microparticles or injury alone. Our results indicate that SDF-1α loaded microparticles may be a novel approach to shift the cellular composition within the supraspinatus muscle and create a more pro-regenerative milieu, which may provide a platform to improve muscle repair following rotator cuff injury in the future.
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Affiliation(s)
- L.E. Tellier
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA
| | - J.R. Krieger
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA
| | - A.L. Brimeyer
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA
| | - A.C. Coogan
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA
| | - A.A. Falis
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA
| | - T.E. Rinker
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA
| | - A. Schudel
- School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA
- Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA
| | - S.N. Thomas
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA
- Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA
- George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA
- Winship Cancer Institute, Emory University, Decatur, GA
| | - C.D. Jarrett
- Wilmington Health Orthopedic Medical Center, Wilmington, NC
- Department of Orthopedics, Emory University, Decatur, GA
| | - N.J. Willett
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA
- Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA
- Department of Orthopedics, Emory University, Decatur, GA
- Atlanta Veteran’s Affairs Medical Center, Decatur, GA
| | - E.A. Botchwey
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA
- Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA
| | - J.S. Temenoff
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA
- Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA
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Gibbons MC, Singh A, Engler AJ, Ward SR. The role of mechanobiology in progression of rotator cuff muscle atrophy and degeneration. J Orthop Res 2018; 36:546-556. [PMID: 28755470 PMCID: PMC5788743 DOI: 10.1002/jor.23662] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 07/24/2017] [Indexed: 02/06/2023]
Abstract
Rotator cuff (RC) muscles undergo several detrimental changes following mechanical unloading resulting from RC tendon tear. In this review, we highlight the pathological causes and consequences of mechanical alterations at the whole muscle, muscle fiber, and muscle resident cell level as they relate to RC disease progression. In brief, the altered mechanical loads associated with RC tear lead to architectural, structural, and compositional changes at the whole-muscle and muscle fiber level. At the cellular level, these changes equate to direct disruption of mechanobiological signaling, which is exacerbated by mechanically regulated biophysical and biochemical changes to the cellular and extra-cellular environment (also known as the stem cell "niche"). Together, these data have important implications for both pre-clinical models and clinical practice. In pre-clinical models, it is important to recapitulate both the atrophic and degenerative muscle loss found in humans using clinically relevant modes of injury. Clinically, understanding the mechanics and underlying biology of the muscle will impact both surgical decision-making and rehabilitation protocols, as interventions that may be good for atrophic muscle will have a detrimental effect on degenerating muscle, and vice versa. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:546-556, 2018.
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Affiliation(s)
| | | | - Adam J Engler
- University of California San Diego Department of Bioengineering
| | - Samuel R Ward
- University of California Department of Orthopedic Surgery,University of California Department of Radiology
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Gumucio JP, Sugg KB, Enselman ERS, Konja AC, Eckhardt LR, Bedi A, Mendias CL. Anterior cruciate ligament tear induces a sustained loss of muscle fiber force production. Muscle Nerve 2018; 58:10.1002/mus.26075. [PMID: 29346717 PMCID: PMC6051936 DOI: 10.1002/mus.26075] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Revised: 01/14/2018] [Accepted: 01/16/2018] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Patients with anterior cruciate ligament (ACL) tears have persistent quadriceps strength deficits that are thought to be due to altered neurophysiological function. Our goal was to determine the changes in muscle fiber contractility independent of the ability of motor neurons to activate fibers. METHODS We obtained quadriceps biopsies of patients undergoing ACL reconstruction, and additional biopsies 1, 2, and 6 months after surgery. Muscles fiber contractility was assessed in vitro, along with whole muscle strength testing. RESULTS Compared with controls, patients had a 30% reduction in normalized muscle fiber force at the time of surgery. One month later, the force deficit was 41%, and at 6 months the deficit was 23%. Whole muscle strength testing demonstrated similar trends. DISCUSSION While neurophysiological dysfunction contributes to whole muscle weakness, there is also a reduction in the force generating capacity of individual muscle cells independent of alpha motor neuron activation. Muscle Nerve, 2018.
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Affiliation(s)
- Jonathan P Gumucio
- Department of Orthopaedic Surgery, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, MI
- Department of Molecular & Integrative Physiology, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, MI
| | - Kristoffer B Sugg
- Department of Orthopaedic Surgery, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, MI
- Department of Molecular & Integrative Physiology, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, MI
- Department of Surgery, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, MI
| | | | - Alexis C Konja
- Department of Orthopaedic Surgery, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, MI
| | - Logan R Eckhardt
- Department of Orthopaedic Surgery, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, MI
| | - Asheesh Bedi
- Department of Orthopaedic Surgery, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, MI
| | - Christopher L Mendias
- Department of Orthopaedic Surgery, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, MI
- Department of Molecular & Integrative Physiology, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, MI
- Hospital for Special Surgery, New York, NY
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Gibbons MC, Fisch KM, Pichika R, Cheng T, Engler AJ, Schenk S, Lane JG, Singh A, Ward SR. Heterogeneous muscle gene expression patterns in patients with massive rotator cuff tears. PLoS One 2018; 13:e0190439. [PMID: 29293645 PMCID: PMC5749784 DOI: 10.1371/journal.pone.0190439] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 12/14/2017] [Indexed: 01/26/2023] Open
Abstract
Detrimental changes in the composition and function of rotator cuff (RC) muscles are hallmarks of RC disease progression. Previous studies have demonstrated both atrophic and degenerative muscle loss in advanced RC disease. However, the relationship between gene expression and RC muscle pathology remains poorly defined, in large part due to a lack of studies correlating gene expression to tissue composition. Therefore, the purpose of this study was to determine how tissue composition relates to gene expression in muscle biopsies from patients undergoing reverse shoulder arthroplasty (RSA). Gene expression related to myogenesis, atrophy and cell death, adipogenesis and metabolism, inflammation, and fibrosis was measured in 40 RC muscle biopsies, including 31 biopsies from reverse shoulder arthroplasty (RSA) cases that had available histology data and 9 control biopsies from patients with intact RC tendons. After normalization to reference genes, linear regression was used to identify relationships between gene expression and tissue composition. Hierarchical clustering and principal component analysis (PCA) identified unique clusters, and fold-change analysis was used to determine significant differences in expression between clusters. We found that gene expression profiles were largely dependent on muscle presence, with muscle fraction being the only histological parameter that was significantly correlated to gene expression by linear regression. Similarly, samples with histologically-confirmed muscle distinctly segregated from samples without muscle. However, two sub-groups within the muscle-containing RSA biopsies suggest distinct phases of disease, with one group expressing markers of both atrophy and regeneration, and another group not significantly different from either control biopsies or biopsies lacking muscle. In conclusion, this study provides context for the interpretation of gene expression in heterogeneous and degenerating muscle, and provides further evidence for distinct stages of RC disease in humans.
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Affiliation(s)
- Michael C. Gibbons
- Department of Bioengineering, University of California San Diego, La Jolla, California, United States of America
| | - Kathleen M. Fisch
- Department of Computational Biology, University of California San Diego, La Jolla, California, United States of America
| | - Rajeswari Pichika
- Department of Orthopedic Surgery, University of California San Diego, La Jolla, California, United States of America
| | - Timothy Cheng
- Department of Orthopedic Surgery, University of California San Diego, La Jolla, California, United States of America
| | - Adam J. Engler
- Department of Bioengineering, University of California San Diego, La Jolla, California, United States of America
| | - Simon Schenk
- Department of Orthopedic Surgery, University of California San Diego, La Jolla, California, United States of America
| | - John G. Lane
- Department of Orthopedic Surgery, University of California San Diego, La Jolla, California, United States of America
| | - Anshu Singh
- Department of Orthopedic Surgery, University of California San Diego, La Jolla, California, United States of America
- Department of Orthopedic Surgery, Kaiser Permanente, San Diego, La Jolla, California, United States of America
| | - Samuel R. Ward
- Department of Orthopedic Surgery, University of California San Diego, La Jolla, California, United States of America
- Department of Radiology, University of California San Diego, La Jolla, California, United States of America
- * E-mail:
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36
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Shah SA, Kormpakis I, Cavinatto L, Killian ML, Thomopoulos S, Galatz LM. Rotator cuff muscle degeneration and tear severity related to myogenic, adipogenic, and atrophy genes in human muscle. J Orthop Res 2017; 35:2808-2814. [PMID: 28470887 PMCID: PMC5671367 DOI: 10.1002/jor.23593] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Accepted: 04/17/2017] [Indexed: 02/04/2023]
Abstract
Large rotator cuff tear size and advanced muscle degeneration can affect reparability of tears and compromise tendon healing. Clinicians often rely on direct measures of rotator cuff tear size and muscle degeneration from magnetic resonance imaging (MRI) to determine whether the rotator cuff tear is repairable. The objective of this study was to identify the relationship between gene expression changes in rotator cuff muscle degeneration to standard data available to clinicians. Radiographic assessment of preoperative rotator cuff tear severity was completed for 25 patients with varying magnitudes of rotator cuff tears. Tear width and retraction were measured using MRI, and Goutallier grade, tangent (tan) sign, and Thomazeau grade were determined. Expression of myogenic-, adipogenic-, atrophy-, and metabolism-related genes in biopsied muscles were correlated with tear width, tear retraction, Goutallier grade, tan sign, and Thomazeau grade. Tear width positively correlated with Goutallier grade in both the supraspinatus (r = 0.73) and infraspinatus (r = 0.77), along with tan sign (r = 0.71) and Thomazeau grade (r = 0.68). Decreased myogenesis (Myf5), increased adipogenesis (CEBPα, Lep, Wnt10b), and decreased metabolism (PPARα) correlated with radiographic assessments. Gene expression changes suggest that rotator cuff tears lead to a dramatic molecular response in an attempt to maintain normal muscle tissue, increase adipogenesis, and decrease metabolism. Fat accumulation and muscle atrophy appear to stem from endogenous changes rather than from changes mediated by infiltrating cells. Results suggest that chronic unloading of muscle, induced by rotator cuff tear, disrupts muscle homeostasis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2808-2814, 2017.
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Affiliation(s)
- Shivam A. Shah
- Department of Orthopaedic Surgery, Washington University in St. Louis, Saint Louis, Missouri
| | - Ioannis Kormpakis
- Department of Orthopaedic Surgery, Washington University in St. Louis, Saint Louis, Missouri
| | - Leonardo Cavinatto
- Department of Orthopaedic Surgery, Icahn School of Medicine, Mount Sinai Health System, 5 East 98th St, 9th floor, New York, New York 10029
| | - Megan L. Killian
- Department of Orthopaedic Surgery, Washington University in St. Louis, Saint Louis, Missouri,Department of Biomedical Engineering, University of Delaware, Newark, Delaware
| | - Stavros Thomopoulos
- Department of Orthopedic Surgery, Columbia University, Black Building 1408, 650 W 168 ST, New York, New York 10032
| | - Leesa M. Galatz
- Department of Orthopaedic Surgery, Icahn School of Medicine, Mount Sinai Health System, 5 East 98th St, 9th floor, New York, New York 10029
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38
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What is the role of systemic conditions and options for manipulation of bone formation and bone resorption in rotator cuff tendon healing and repair? TECHNIQUES IN SHOULDER AND ELBOW SURGERY 2017; 18:113-120. [PMID: 28966557 DOI: 10.1097/bte.0000000000000121] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Rotator cuff pathology is a significant cause of shoulder pain. Operative repair of rotator cuff is an established standard of care for these patient, however, failure of the procedure is common. Systemic conditions such as diabetes mellitus, hypocholesteremia, thyroid disease, and smoking significantly affect the outcomes of rotator cuff repair and have significant implications for the management of these patients. Diabetes mellitus has been proposed to damage tendons through non-enzymatic glycosylation of collagen with advanced glycation end product formation and impaired microcirculation. Hypocholesteremia may lead to fatty infiltration and subsequent pro-inflammatory degenerative enzymatic degeneration. Thyroid disease may disrupt tendon homeostasis through the alteration of collagen production and the accumulation of glycosaminoglycans. Lastly, smoking inhibits tendon healing through the induction of hypovascularity and hypoperfusion. Understanding of the implications these systemic conditions have on the outcomes is important in the management of rotator cuff disease.
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Shen H, Lim C, Schwartz AG, Andreev-Andrievskiy A, Deymier AC, Thomopoulos S. Effects of spaceflight on the muscles of the murine shoulder. FASEB J 2017; 31:5466-5477. [PMID: 28821629 DOI: 10.1096/fj.201700320r] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Accepted: 07/31/2017] [Indexed: 12/31/2022]
Abstract
Mechanical loading is necessary for the development and maintenance of the musculoskeletal system. Removal of loading via microgravity, paralysis, or bed rest leads to rapid loss of muscle mass and function; however, the molecular mechanisms that lead to these changes are largely unknown, particularly for the spaceflight (SF) microgravity environment. Furthermore, few studies have explored these effects on the shoulder, a dynamically stabilized joint with a large range of motion; therefore, we examined the effects of microgravity on mouse shoulder muscles for the 15-d Space Transportation System (STS)-131, 13-d STS-135, and 30-d Bion-M1 missions. Mice from STS missions were euthanized within 4 h after landing, whereas mice from the Bion-M1 mission were euthanized within 14 h after landing. The motion-generating deltoid muscle was more sensitive to microgravity than the joint-stabilizing rotator cuff muscles. Mice from the STS-131 mission exhibited reduced myogenic (Myf5 and -6) and adipogenic (Pparg, Cebpa, and Lep) gene expression, whereas either no change or an increased expression of these genes was observed in mice from the Bion-M1 mission. In summary, muscle responses to microgravity were muscle-type specific, short-duration SF caused dramatic molecular changes to shoulder muscles and responses to reloading upon landing were rapid.-Shen, H., Lim, C., Schwartz, A. G., Andreev-Andrievskiy, A., Deymier, A. C., Thomopoulos, S. Effects of spaceflight on the muscles of the murine shoulder.
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Affiliation(s)
- Hua Shen
- Department of Orthopaedic Surgery, Washington University, St. Louis, Missouri, USA
| | - Chanteak Lim
- Department of Orthopaedic Surgery, Washington University, St. Louis, Missouri, USA
| | - Andrea G Schwartz
- Department of Orthopaedic Surgery, Washington University, St. Louis, Missouri, USA
| | - Alexander Andreev-Andrievskiy
- Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia.,Biology Faculty, M.V. Lomonosov Moscow State University, Moscow, Russia
| | - Alix C Deymier
- Department of Orthopedic Surgery, Columbia University, New York, New York, USA
| | - Stavros Thomopoulos
- Department of Orthopedic Surgery, Columbia University, New York, New York, USA; .,Department of Biomedical Engineering, Columbia University, New York, New York, USA
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Quantitative analysis of immune cell subset infiltration of supraspinatus muscle after severe rotator cuff injury. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2017; 3:82-93. [PMID: 28706969 DOI: 10.1007/s40883-017-0030-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Rotator cuff tears cause muscle degeneration that is characterized by myofiber atrophy, fatty infiltration, and fibrosis and is minimally responsive to current treatment options. The underlying pathogenesis of rotator cuff muscle degeneration remains to be elucidated, and increasing evidence implicates immune cell infiltration as a significant factor. Because immune cells are comprised of highly heterogeneous subpopulations that exert divergent effects on injured tissue, understanding trafficking and accumulation of immune subpopulations may hold the key to more effective therapies. The present study quantifies subpopulations of immune cells infiltrating the murine supraspinatus muscle after severe rotator cuff injury that includes tenotomy and denervation. Rotator cuff injury stimulates dramatic infiltration of mononuclear phagocytes, enriches mononuclear phagocytes in non-classical subpopulations, and enriches T lymphocytes in TH and Treg subpopulations. The combination of tenotomy plus denervation significantly increases mononuclear phagocyte infiltration, enriches macrophages in the non-classical subpopulation, and decreases T lymphocyte enrichment in TH cells compared to tenotomy alone. Depletion of circulating monocytes via liposomal clodronate accelerates supraspinatus atrophy after tenotomy and denervation. The study may aid rational design of immunologically smart therapies that harness immune cells to enhance outcomes after rotator cuff tears.
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Liu M, Lee C, Laron D, Zhang N, Waldorff EI, Ryaby JT, Feeley B, Liu X. Role of pulsed electromagnetic fields (PEMF) on tenocytes and myoblasts-potential application for treating rotator cuff tears. J Orthop Res 2017; 35:956-964. [PMID: 27138553 DOI: 10.1002/jor.23278] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 04/25/2016] [Indexed: 02/04/2023]
Abstract
The post-surgery integrity of the tendons and muscle quality are the two major factors in success of rotator cuff (RC) repair. Though surgical techniques for rotator cuff repair have significantly improved in the past two decades, there are no effective treatments to improve tendon-to-bone healing and muscle quality after repair at this point in time. Pulsed electromagnetic fields (PEMF) have previously been used for promoting fracture healing. Previous studies have shown that PEMF has a positive role in promoting osteoblast precursors proliferation and differentiation. However, PEMFs effect on tenocytes and muscle cells has not been determined fully yet. The purpose of this study is to define the role of a commercially available PEMF on tenocytes and myoblasts growth and differentiation in vitro. Human rotator cuff tenocytes and C2C12 murine myoblasts were cultured and treated with PEMF for 2 weeks under regular and inflammatory conditions. Our results showed that 2 weeks treatment of PEMF enhanced gene expressions of growth factors in human rotator cuff tenocytes under inflammatory conditions. PEMF significantly enhanced C2C12 myotube formation under normal and inflammatory conditions. Results from this study suggest that PEMF has a positive role in promoting tenocyte gene expression and myoblast differentiation. Therefore, PEMF may potentially serve as a non-operative treatment to improve clinical incomes rotator cuff tendon repairs. Results © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:956-964, 2017.
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Affiliation(s)
- Mengyao Liu
- Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, 1700 Owens Street, Room 364, San Francisco, California, 94153.,Department of Orthopaedic Surgery, University of California, San Francisco, California
| | - Carlin Lee
- Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, 1700 Owens Street, Room 364, San Francisco, California, 94153.,Department of Orthopaedic Surgery, University of California, San Francisco, California
| | - Dominique Laron
- Department of Orthopaedic Surgery, University of California, San Francisco, California
| | | | | | | | - Brian Feeley
- Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, 1700 Owens Street, Room 364, San Francisco, California, 94153.,Department of Orthopaedic Surgery, University of California, San Francisco, California
| | - Xuhui Liu
- Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, 1700 Owens Street, Room 364, San Francisco, California, 94153.,Department of Orthopaedic Surgery, University of California, San Francisco, California
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Rothrauff BB, Pauyo T, Debski RE, Rodosky MW, Tuan RS, Musahl V. The Rotator Cuff Organ: Integrating Developmental Biology, Tissue Engineering, and Surgical Considerations to Treat Chronic Massive Rotator Cuff Tears. TISSUE ENGINEERING PART B-REVIEWS 2017; 23:318-335. [PMID: 28084902 DOI: 10.1089/ten.teb.2016.0446] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The torn rotator cuff remains a persistent orthopedic challenge, with poor outcomes disproportionately associated with chronic, massive tears. Degenerative changes in the tissues that comprise the rotator cuff organ, including muscle, tendon, and bone, contribute to the poor healing capacity of chronic tears, resulting in poor function and an increased risk for repair failure. Tissue engineering strategies to augment rotator cuff repair have been developed in an effort to improve rotator cuff healing and have focused on three principal aims: (1) immediate mechanical augmentation of the surgical repair, (2) restoration of muscle quality and contractility, and (3) regeneration of native enthesis structure. Work in these areas will be reviewed in sequence, highlighting the relevant pathophysiology, developmental biology, and biomechanics, which must be considered when designing therapeutic applications. While the independent use of these strategies has shown promise, synergistic benefits may emerge from their combined application given the interdependence of the tissues that constitute the rotator cuff organ. Furthermore, controlled mobilization of augmented rotator cuff repairs during postoperative rehabilitation may provide mechanotransductive cues capable of guiding tissue regeneration and restoration of rotator cuff function. Present challenges and future possibilities will be identified, which if realized, may provide solutions to the vexing condition of chronic massive rotator cuff tears.
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Affiliation(s)
- Benjamin B Rothrauff
- 1 Department of Orthopaedic Surgery, Center for Cellular and Molecular Engineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Thierry Pauyo
- 3 Division of Sports Medicine, Department of Orthopaedic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Richard E Debski
- 2 McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Mark W Rodosky
- 3 Division of Sports Medicine, Department of Orthopaedic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Rocky S Tuan
- 1 Department of Orthopaedic Surgery, Center for Cellular and Molecular Engineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Volker Musahl
- 2 McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.,3 Division of Sports Medicine, Department of Orthopaedic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.,4 Orthopaedic Robotics Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania
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Gibbons MC, Singh A, Anakwenze O, Cheng T, Pomerantz M, Schenk S, Engler AJ, Ward SR. Histological Evidence of Muscle Degeneration in Advanced Human Rotator Cuff Disease. J Bone Joint Surg Am 2017; 99:190-199. [PMID: 28145949 PMCID: PMC5395080 DOI: 10.2106/jbjs.16.00335] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Cellular remodeling in rotator cuff muscles following a massive rotator cuff tear is poorly understood. The aim of the current study was to provide histological evidence to elucidate the mode of muscle loss in advanced human rotator cuff disease and to assess tissue-level changes in relation to findings on noninvasive imaging. METHODS Rotator cuff muscle biopsy samples were taken from the scapular fossae from 23 consecutive patients undergoing reverse total shoulder arthroplasty in order to evaluate muscle composition in severe rotator cuff disease. Markers of vascularity; inflammation; fat distribution; and muscle atrophy, degeneration, and regeneration were quantified. RESULTS The samples primarily consisted of dense, organized connective tissue (48.2% ± 19.1%) and disorganized, loose connective tissue (36.9% ± 15.9%), with substantially smaller fractions of muscle (10.4% ± 22.0%) and fat (6.5% ± 11.6%). Only 25.8% of the biopsy pool contained any muscle fibers at all. Increased inflammatory cell counts (111.3 ± 81.5 macrophages/mm) and increased vascularization (66.6 ± 38.0 vessels/mm) were observed across biopsies. Muscle fiber degeneration was observed in 90.0% ± 15.6% of observable muscle fascicles, and the percentage of centrally nucleated muscle fibers was pathologically elevated (11.3% ± 6.3%). Fat accumulation was noted in both perifascicular (60.7% ± 41.4%) and intrafascicular (42.2% ± 33.6%) spaces, with evidence that lipid may replace contractile elements without altering muscle organization. CONCLUSIONS Dramatic degeneration and inflammation of the rotator cuff muscles are characteristics of the most chronic and severe rotator cuff disease states, suggesting that muscle loss is more complicated than, and distinct from, the simple atrophy found in less severe cases. CLINICAL RELEVANCE In order to address degenerative muscle loss, alternative therapeutic approaches directed at muscle regeneration must be considered if muscle function is to be restored in late-stage rotator cuff disease.
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Affiliation(s)
- Michael C. Gibbons
- Departments of Bioengineering (M.C.G. and A.J.E.), Orthopaedic Surgery (T.C., M.P., S.S., and S.R.W.), and Radiology (S.R.W.), University of California San Diego, San Diego, California
| | | | | | - Timothy Cheng
- Departments of Bioengineering (M.C.G. and A.J.E.), Orthopaedic Surgery (T.C., M.P., S.S., and S.R.W.), and Radiology (S.R.W.), University of California San Diego, San Diego, California
| | - Maxwill Pomerantz
- Departments of Bioengineering (M.C.G. and A.J.E.), Orthopaedic Surgery (T.C., M.P., S.S., and S.R.W.), and Radiology (S.R.W.), University of California San Diego, San Diego, California
| | - Simon Schenk
- Departments of Bioengineering (M.C.G. and A.J.E.), Orthopaedic Surgery (T.C., M.P., S.S., and S.R.W.), and Radiology (S.R.W.), University of California San Diego, San Diego, California
| | - Adam J. Engler
- Departments of Bioengineering (M.C.G. and A.J.E.), Orthopaedic Surgery (T.C., M.P., S.S., and S.R.W.), and Radiology (S.R.W.), University of California San Diego, San Diego, California
| | - Samuel R. Ward
- Departments of Bioengineering (M.C.G. and A.J.E.), Orthopaedic Surgery (T.C., M.P., S.S., and S.R.W.), and Radiology (S.R.W.), University of California San Diego, San Diego, California,E-mail address for S.R. Ward:
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Mendias CL, Schwartz AJ, Grekin JA, Gumucio JP, Sugg KB. Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy. J Appl Physiol (1985) 2016; 122:571-579. [PMID: 27979985 DOI: 10.1152/japplphysiol.00719.2016] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 11/04/2016] [Accepted: 12/08/2016] [Indexed: 12/26/2022] Open
Abstract
Skeletal muscle can adapt to increased mechanical loads by undergoing hypertrophy. Transient reductions in whole muscle force production have been reported during the onset of hypertrophy, but contractile changes in individual muscle fibers have not been previously studied. Additionally, the extracellular matrix (ECM) stores and transmits forces from muscle fibers to tendons and bones, and determining how the ECM changes during hypertrophy is important in understanding the adaptation of muscle tissue to mechanical loading. Using the synergist ablation model, we sought to measure changes in muscle fiber contractility, collagen content, and cross-linking, and in the expression of several genes and activation of signaling proteins that regulate critical components of myogenesis and ECM synthesis and remodeling during muscle hypertrophy. Tissues were harvested 3, 7, and 28 days after induction of hypertrophy, and nonoverloaded rats served as controls. Muscle fiber specific force (sFo), which is the maximum isometric force normalized to cross-sectional area, was reduced 3 and 7 days after the onset of mechanical overload, but returned to control levels by 28 days. Collagen abundance displayed a similar pattern of change. Nearly a quarter of the transcriptome changed over the course of overload, as well as the activation of signaling pathways related to hypertrophy and atrophy. Overall, this study provides insight into fundamental mechanisms of muscle and ECM growth, and indicates that although muscle fibers appear to have completed remodeling and regeneration 1 mo after synergist ablation, the ECM continues to be actively remodeling at this time point.NEW & NOTEWORTHY This study utilized a rat synergist ablation model to integrate changes in single muscle fiber contractility, extracellular matrix composition, activation of important signaling pathways in muscle adaption, and corresponding changes in the muscle transcriptome to provide novel insight into the basic biological mechanisms of muscle fiber hypertrophy.
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Affiliation(s)
- Christopher L Mendias
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan; .,Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan; and
| | - Andrew J Schwartz
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan; and
| | - Jeremy A Grekin
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Jonathan P Gumucio
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan.,Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan; and
| | - Kristoffer B Sugg
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan.,Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan; and.,Department of Surgery, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
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Butt U, Rashid MS, Temperley D, Crank S, Birch A, Freemont AJ, Trail IA. Muscle regeneration following repair of the rotator cuff. Bone Joint J 2016; 98-B:1389-1394. [DOI: 10.1302/0301-620x.98b10.37231] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Accepted: 06/29/2016] [Indexed: 11/05/2022]
Abstract
Aims The aim of this study was to analyse human muscle tissue before and after rotator cuff repair to look for evidence of regeneration, and to characterise the changes seen in the type of muscle fibre. Patients and Methods Patients were assessed pre-operatively and one year post-operatively using the Oxford Shoulder Score (OSS) and MRI. The cross-sectional area and distribution of the type of muscle fibre were assessed on biopsies, which were taken at surgery and one year post-operatively. Paired samples from eight patients were analysed. There were three men and five women with a mean age of 63 years (50 to 73). Results All but one patient showed improvement in OSS (p = 0.004). The mean increase in the cross-sectional area of the muscle was 1220 μm2 (-801 to 3712; p = 0.03). There was a reduction of type 2a fibres (p = 0.02). A clear relationship could not be seen between the MRI findings and the histological appearances. Conclusion This is the first study to provide evidence that atrophy of the supraspinatus muscle is reversible. Changes in the types of fibre are discussed. MRI assessment of muscle atrophy may not be fully representative of myofibre atrophy. Cite this article: Bone Joint J 2016;98-B:1389–94.
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Affiliation(s)
- U. Butt
- Salford Royal NHS Foundation Trust, Salford, UK
| | - M. S. Rashid
- Royal London Hospital, Whitechapel
Road, London, E1 1BB, UK
| | - D. Temperley
- Wrightington Hospital, Hall
Lane, Appley Bridge, Wigan, Lancashire, WN6
9EP, UK
| | - S. Crank
- Wrightington Hospital, Hall
Lane, Appley Bridge, Wigan, Lancashire, WN6
9EP, UK
| | - A. Birch
- Wrightington Hospital, Hall
Lane, Appley Bridge, Wigan, Lancashire, WN6
9EP, UK
| | - A. J. Freemont
- University of Manchester and Manchester
Academic Health Sciences Centre, Stopford
Building, Oxford Road, Manchester, M13 9PT, UK
| | - I. A. Trail
- Wrightington Hospital, Hall
Lane, Appley Bridge, Wigan, Lancashire, WN6
9EP, UK
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Wilde JM, Gumucio JP, Grekin JA, Sarver DC, Noah AC, Ruehlmann DG, Davis ME, Bedi A, Mendias CL. Inhibition of p38 mitogen-activated protein kinase signaling reduces fibrosis and lipid accumulation after rotator cuff repair. J Shoulder Elbow Surg 2016; 25:1501-8. [PMID: 27068389 PMCID: PMC4992438 DOI: 10.1016/j.jse.2016.01.035] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 01/16/2016] [Accepted: 01/22/2016] [Indexed: 02/01/2023]
Abstract
BACKGROUND The repair of rotator cuff tears is often complicated by fatty degeneration, which is the combination of lipid accumulation, fibrosis, inflammation, and muscle weakness. A signaling molecule that plays a central role in these processes is p38 mitogen-activated protein kinase (MAPK). The purpose of this study was to evaluate the ability of a small molecule inhibitor of p38 MAPK, SB203580, to reduce fatty degeneration in a preclinical model of rotator cuff injury and repair. MATERIALS AND METHODS Adult rats underwent a bilateral supraspinatus tenotomy that was repaired 30 days later. Rats were treated with SB203580 or vehicle every 2 days, with injections beginning 3 days before surgery and continuing until 7 days after surgery. Two weeks after surgical repair, muscles were analyzed using histology, lipid profiling, gene expression, and permeabilized muscle fiber contractility. RESULTS Inhibition of p38 MAPK resulted in a nearly 49% reduction in fat accumulation and a 29% reduction in collagen content, along with changes in corresponding genes regulating adipogenesis and matrix accumulation. There was also a marked 40% to 80% decrease in the expression of several proinflammatory genes, including IL1B, IL6, and COX2, and a 360% increase in the anti-inflammatory gene IL10. No differences were observed for muscle fiber force production. CONCLUSION Inhibition of p38 MAPK was found to result in a significant decrease in intramuscular lipid accumulation and fibrosis that is usually seen in the degenerative cascade of rotator cuff tears, without having negative effects on the contractile properties of the rotator cuff muscle tissue.
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Affiliation(s)
- Jeffrey M Wilde
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Jonathan P Gumucio
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA,Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Jeremy A Grekin
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Dylan C Sarver
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Andrew C Noah
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - David G Ruehlmann
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Max E Davis
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Asheesh Bedi
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Christopher L Mendias
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA,Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA,Corresponding Author: Christopher L. Mendias, PhD, ATC, Department of Orthopaedic Surgery, University of Michigan Medical School, 109 Zina Pitcher Place, BSRB 2017, Ann Arbor, MI 48109-2200, USA,
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When Is the Rotator Cuff Not Repairable? Tech Orthop 2016. [DOI: 10.1097/bto.0000000000000171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Claflin DR, Roche SM, Gumucio JP, Mendias CL, Brooks SV. Assessment of the Contractile Properties of Permeabilized Skeletal Muscle Fibers. Methods Mol Biol 2016; 1460:321-36. [PMID: 27492182 PMCID: PMC11423931 DOI: 10.1007/978-1-4939-3810-0_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]
Abstract
Permeabilized individual skeletal muscle fibers offer the opportunity to evaluate contractile behavior in a system that is greatly simplified, yet physiologically relevant. Here we describe the steps required to prepare, permeabilize and preserve small samples of skeletal muscle. We then detail the procedures used to isolate individual fiber segments and attach them to an experimental apparatus for the purpose of controlling activation and measuring force generation. We also describe our technique for estimating the cross-sectional area of fiber segments. The area measurement is necessary for normalizing the absolute force to obtain specific force, a measure of the intrinsic force-generating capability of the contractile system.
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Affiliation(s)
- Dennis R Claflin
- Department of Surgery, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
- Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA
| | - Stuart M Roche
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Jonathan P Gumucio
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
- Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Christopher L Mendias
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
- Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Susan V Brooks
- Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA.
- Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
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Sambandam SN, Khanna V, Gul A, Mounasamy V. Rotator cuff tears: An evidence based approach. World J Orthop 2015; 6:902-918. [PMID: 26716086 PMCID: PMC4686437 DOI: 10.5312/wjo.v6.i11.902] [Citation(s) in RCA: 125] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2015] [Revised: 08/04/2015] [Accepted: 10/19/2015] [Indexed: 02/06/2023] Open
Abstract
Lesions of the rotator cuff (RC) are a common occurrence affecting millions of people across all parts of the globe. RC tears are also rampantly prevalent with an age-dependent increase in numbers. Other associated factors include a history of trauma, limb dominance, contralateral shoulder, smoking-status, hypercholesterolemia, posture and occupational dispositions. The challenge lies in early diagnosis since a high proportion of patients are asymptomatic. Pain and decreasing shoulder power and function should alert the heedful practitioner in recognizing promptly the onset or aggravation of existing RC tears. Partial-thickness tears (PTT) can be bursal-sided or articular-sided tears. Over the course of time, PTT enlarge and propagate into full-thickness tears (FTT) and develop distinct chronic pathological changes due to muscle retraction, fatty infiltration and muscle atrophy. These lead to a reduction in tendon elasticity and viability. Eventually, the glenohumeral joint experiences a series of degenerative alterations - cuff tear arthropathy. To avert this, a vigilant clinician must utilize and corroborate clinical skill and radiological findings to identify tear progression. Modern radio-diagnostic means of ultrasonography and magnetic resonance imaging provide excellent visualization of structural details and are crucial in determining further course of action for these patients. Physical therapy along with activity modifications, anti-inflammatory and analgesic medications form the pillars of nonoperative treatment. Elderly patients with minimal functional demands can be managed conservatively and reassessed at frequent intervals. Regular monitoring helps in isolating patients who require surgical interventions. Early surgery should be considered in younger, active and symptomatic, healthy patients. In addition to being cost-effective, this helps in providing a functional shoulder with a stable cuff. An easily reproducible technique of maximal strength and sturdiness should by chosen among the armamentarium of the shoulder surgeon. Grade 1 PTTs do well with debridement while more severe lesions mandate repair either by trans-tendon technique or repair following conversion into FTT. Early repair of repairable FTT can avoid appearance and progression of disability and weakness. The choice of surgery varies from surgeon-to-surgeon with arthroscopy taking the lead in the current scenario. The double-row repairs have an edge over the single-row technique in some patients especially those with massive tears. Stronger, cost-effective and improved functional scores can be obtained by the former. Both early and delayed postoperative rehabilitation programmes have led to comparable outcomes. Guarded results may be anticipated in patients in extremes of age, presence of comorbidities and severe tear patters. Overall, satisfactory results are obtained with timely diagnosis and execution of the appropriate treatment modality.
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Change in the Pathologic Supraspinatus: A Three-Dimensional Model of Fiber Bundle Architecture within Anterior and Posterior Regions. BIOMED RESEARCH INTERNATIONAL 2015; 2015:564825. [PMID: 26413533 PMCID: PMC4564630 DOI: 10.1155/2015/564825] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Revised: 04/02/2015] [Accepted: 04/03/2015] [Indexed: 11/21/2022]
Abstract
Supraspinatus tendon tears are common and lead to changes in the muscle architecture. To date, these changes have not been investigated for the distinct regions and parts of the pathologic supraspinatus. The purpose of this study was to create a novel three-dimensional (3D) model of the muscle architecture throughout the supraspinatus and to compare the architecture between muscle regions and parts in relation to tear severity. Twelve cadaveric specimens with varying degrees of tendon tears were used. Three-dimensional coordinates of fiber bundles were collected in situ using serial dissection and digitization. Data were reconstructed and modeled in 3D using Maya. Fiber bundle length (FBL) and pennation angle (PA) were computed and analyzed. FBL was significantly shorter in specimens with large retracted tears compared to smaller tears, with the deeper fibers being significantly shorter than other parts in the anterior region. PA was significantly greater in specimens with large retracted tears, with the superficial fibers often demonstrating the largest PA. The posterior region was absent in two specimens with extensive tears. Architectural changes associated with tendon tears affect the regions and varying depths of supraspinatus differently. The results provide important insights on residual function of the pathologic muscle, and the 3D model includes detailed data that can be used in future modeling studies.
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