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Kaneguchi A, Yamaoka K, Ozawa J. Long-term observation of marrow adipose tissue and trabecular bone in the rat proximal tibial epiphysis after anterior cruciate ligament reconstruction: effects of immobilization and non-weightbearing. Biotech Histochem 2025; 100:72-82. [PMID: 40008463 DOI: 10.1080/10520295.2025.2470622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2025] Open
Abstract
Anterior cruciate ligament (ACL) injury and subsequent reconstruction induce marrow adipose tissue (MAT) accumulation accompanied by bone loss. Short-term immobilization or non-weightbearing after ACL reconstruction further promotes MAT accumulation. However, it is unclear if combining immobilization and non-weightbearing synergistically promotes MAT accumulation. Additionally, it is unknown whether MAT increase induced by immobilization or non-weightbearing can be reversed through remobilization or reloading. We aimed to address these questions. ACL-reconstructed rats were divided into four groups: no intervention, immobilization, non-weightbearing, or immobilization plus non-weightbearing. Immobilization and non-weightbearing were applied for 2 weeks, after which all rats were allowed to move unrestricted. Intact rats were used as controls. The marrow adiposity and trabecular bone in the proximal tibia were histologically assessed at 2-, 4-, and 12-weeks post-surgery. ACL reconstruction induced MAT accumulation and trabecular bone loss accompanied by increased osteoclastogenesis. Two weeks of immobilization and non-weightbearing after ACL reconstruction individually promoted MAT accumulation, but the combined use of these interventions had a similar impact on MAT accumulation as either of each intervention. Importantly, the increased MAT induced by immobilization or non-weightbearing did not reverse even after remobilization or reloading. Neither immobilization, non-weightbearing, nor both conditions combined after ACL reconstruction further decreased trabecular bone compared to no intervention. These findings suggest no synergistic effect of immobilization and non-weightbearing on MAT accumulation, and MAT accumulation induced by 2 weeks of both immobilization or non-weightbearing did not decrease even after at least 10 weeks of remobilization or reloading. MAT accumulation due to both immobilization and non-weightbearing did not have negative effects on trabecular bone.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan
| | - Junya Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan
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Miltenberg B, Martinazzi BJ, Monahan PF, Johns WL, Onor G, Faasuamalie PE, Toci GR, Aynardi MC, Ciccotti MG. Perioperative Losartan Is Associated With Similar Rates of Additional Surgical Procedures for Postoperative Shoulder Stiffness After Primary Arthroscopic Rotator Cuff Repair but Lower Rates of Secondary Debridement and Repair. Arthroscopy 2024:S0749-8063(24)01014-4. [PMID: 39631477 DOI: 10.1016/j.arthro.2024.11.084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 11/15/2024] [Accepted: 11/17/2024] [Indexed: 12/07/2024]
Abstract
PURPOSE To compare the rate of additional shoulder surgery related to postoperative stiffness or tendon healing after primary rotator cuff repair between patients with a losartan prescription and without a losartan prescription. METHODS The International Classification of Diseases, Tenth Revision, code M75.1 was used to identify all patients in the TriNetX Research Network with a rotator cuff tear diagnosis who underwent arthroscopic rotator cuff repair between January 1, 2015, and December 31, 2021. Patients were stratified into the losartan group (LG) and nonlosartan group (NLG) on the basis of whether they had a coded prescription for losartan within 1 year before surgery or 3 months after surgery. The 2 cohorts were propensity scored and matched to reduce confounding biases. Specifically, cohorts were matched on the basis of age, gender, obesity, nicotine use, hyperlipidemia, diabetes, hypertensive diseases, ischemic heart disease, heart failure and valvular disease, and peripheral arterial disease. The incidence of additional shoulder surgeries associated with stiffness and rotator cuff healing was analyzed and compared at 1-year and 2-year time points. RESULTS After propensity score matching, both the LG and NLG contained 3,970 patients. There was no difference in the rate of lysis of adhesions or manipulation under anesthesia at 1-or 2-year postoperatively between patients in the LG and LG. Patients in the LG were less likely undergo arthroscopic debridement (odds ratio 0.71; confidence interval 0.56-0.91; P = .006) and rotator cuff repair (odds ratio 0.71; confidence interval 0.58-0.87; P = .001) 1-year postoperatively than patients in the NLG group. At 1-year postoperatively, there was no difference in the rate of arthroplasty, arthroscopic synovectomy, and diagnostic arthroscopy between groups. At 2-year postoperatively, there was no difference in the rate of rotator cuff repair, arthroplasty, arthroscopic debridement, synovectomy, and diagnostic arthroscopy between groups. CONCLUSIONS Patients undergoing arthroscopic rotator cuff repair with or without a perioperative prescription for losartan had no significant difference in the rate of lysis of adhesions or manipulation under anesthesia at 1- or 2-year postoperatively, indicating that the antifibrotic properties of losartan may not have a clinically significant impact on shoulder stiffness after arthroscopic rotator cuff repair. However, patients with a prescription for losartan were less likely to undergo additional arthroscopic debridement and rotator cuff repair 1-year postoperatively than a matched cohort of patients without a prescription for losartan. LEVEL OF EVIDENCE Level III, case control study.
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Affiliation(s)
- Benjamin Miltenberg
- Rothman Orthopaedic Institute at Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A..
| | - Brandon J Martinazzi
- Rothman Orthopaedic Institute at Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A
| | - Peter F Monahan
- Penn State Health, Milton S. Hershey Medical Center, Hershey, Pennsylvania, U.S.A.; Penn State College of Medicine, Hershey, Pennsylvania, U.S.A
| | - William L Johns
- Rothman Orthopaedic Institute at Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A
| | - Gabriel Onor
- Rothman Orthopaedic Institute at Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A
| | - Paige E Faasuamalie
- Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A
| | - Gregory R Toci
- Rothman Orthopaedic Institute at Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A
| | - Michael C Aynardi
- Penn State Health, Milton S. Hershey Medical Center, Hershey, Pennsylvania, U.S.A.; Penn State College of Medicine, Hershey, Pennsylvania, U.S.A
| | - Michael G Ciccotti
- Rothman Orthopaedic Institute at Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A
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Zhang QB, Huo L, Li M, Zhang R, Zhou T, Wang F, Zhou Y. Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats. Eur J Med Res 2024; 29:298. [PMID: 38802976 PMCID: PMC11129407 DOI: 10.1186/s40001-024-01890-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 05/20/2024] [Indexed: 05/29/2024] Open
Abstract
Joint contracture is one of the common diseases clinically, and joint capsule fibrosis is considered to be one of the most important pathological changes of joint contracture. However, the underlying mechanism of joint capsule fibrosis is still controversial. The present study aims to establish an animal model of knee extending joint contracture in rats, and to investigate the role of hypoxia-mediated pyroptosis in the progression of joint contracture using this animal model. 36 male SD rats were selected, 6 of which were not immobilized and were used as control group, while 30 rats were divided into I-1 group (immobilized for 1 week following 7 weeks of free movement), I-2 group (immobilized for 2 weeks following 6 weeks of free movement), I-4 group (immobilized for 4 weeks following 4 weeks of free movement), I-6 group (immobilized for 6 weeks following 2 weeks of free movement) and I-8 group (immobilized for 8 weeks) according to different immobilizing time. The progression of joint contracture was assessed by the measurement of knee joint range of motion, collagen deposition in joint capsule was examined with Masson staining, protein expression levels of HIF-1α, NLRP3, Caspase-1, GSDMD-N, TGF-β1, α-SMA and p-Smad3 in joint capsule were assessed using western blotting, and the morphological changes of fibroblasts were observed by transmission electron microscopy. The degree of total and arthrogenic contracture progressed from the first week and lasted until the first eight weeks after immobilization. The degree of total and arthrogenic contracture progressed rapidly in the first four weeks after immobilization and then progressed slowly. Masson staining indicated that collagen deposition in joint capsule gradually increased in the first 8 weeks following immobilization. Western blotting analysis showed that the protein levels of HIF-1α continued to increase during the first 8 weeks of immobilization, and the protein levels of pyroptosis-related proteins NLRP3, Caspase-1, GSDMD-N continued to increase in the first 4 weeks after immobilization and then decreased. The protein levels of fibrosis-related proteins TGF-β1, p-Smad3 and α-SMA continued to increase in the first 8 weeks after immobilization. Transmission electron microscopy showed that 4 weeks of immobilization induced cell membrane rupture and cell contents overflow, which further indicated the activation of pyroptosis. Knee extending joint contracture animal model can be established by external immobilization orthosis in rats, and the activation of hypoxia-mediated pyroptosis may play a stimulating role in the process of joint capsule fibrosis and joint contracture.
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Affiliation(s)
- Quan-Bing Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Economic and Technological Development Zone, Hefei, 230601, Anhui, China
| | - Lei Huo
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Economic and Technological Development Zone, Hefei, 230601, Anhui, China
| | - Mian Li
- Hefei Institute of Physical Sciences, Chinese Academy of Sciences, Hefei, 230031, Anhui, China
| | - Rui Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Economic and Technological Development Zone, Hefei, 230601, Anhui, China
| | - Ting Zhou
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Economic and Technological Development Zone, Hefei, 230601, Anhui, China
| | - Feng Wang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Economic and Technological Development Zone, Hefei, 230601, Anhui, China
| | - Yun Zhou
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Economic and Technological Development Zone, Hefei, 230601, Anhui, China.
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Kaneguchi A, Masuhara N, Okahara R, Doi Y, Yamaoka K, Umehara T, Ozawa J. Long-term effects of non-weight bearing and immobilization after anterior cruciate ligament reconstruction on joint contracture formation in rats. Connect Tissue Res 2024; 65:187-201. [PMID: 38517297 DOI: 10.1080/03008207.2024.2331567] [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] [Received: 07/19/2023] [Accepted: 03/12/2024] [Indexed: 03/23/2024]
Abstract
PURPOSE Non-weight bearing improves and immobilization worsens contracture induced by anterior cruciate ligament reconstruction (ACLR), but effect persistence after reloading and remobilization remains unclear, and the combined effects of these factors on ACLR-induced contracture are unknown. We aimed to determine 1) whether the effects of short-term (2-week) non-weight bearing or immobilization after ACLR on contracture would be sustained by reloading or remobilization during a 10-week observation period, and 2) how the combination of both interventions compared to the outcome of either alone. METHODS We divided 88 ACL-reconstructed male rats into four groups: non-intervention, non-weight bearing, joint immobilization, and both interventions. Interventions were performed for 2 weeks, followed by rearing without intervention. Twelve untreated rats were used as controls. At 2, 4, and 12 weeks post-surgery, we assessed range of motion (ROM) and histological changes. RESULTS ACLR resulted in persistent loss of ROM, accompanied by synovial shortening, capsule thickening, and osteophyte formation. Two weeks of non-weight bearing increased ROM and reduced osteophyte size, but the beneficial effects disappeared within 10 weeks after reloading. Two-week immobilization decreased ROM and facilitated synovial shortening. After remobilization, ROM partially recovered but remained below non-intervention levels at 12 weeks. When both interventions were combined, ROM was similar to immobilization alone. CONCLUSIONS The beneficial effects of 2-week non-weight bearing on contracture diminished within 10 weeks after reloading. The adverse effects of 2-week immobilization on contracture persisted after 10 weeks of remobilization. The effects of the combined use of both interventions on contracture were primarily determined by immobilization.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Hiroshima, Japan
| | - Nanami Masuhara
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Hiroshima, Japan
| | - Ryo Okahara
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Hiroshima, Japan
| | - Yoshika Doi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Hiroshima, Japan
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Hiroshima, Japan
| | - Takuya Umehara
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Hiroshima, Japan
| | - Junya Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Hiroshima, Japan
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Kaneguchi A, Yamaoka K, Ozawa J. The Effects of Corticosteroid Administration and Treadmill Exercise on Marrow Adipose Tissue and Trabecular Bone after Anterior Cruciate Ligament Reconstruction in Rats. Acta Histochem Cytochem 2024; 57:47-55. [PMID: 38463208 PMCID: PMC10918434 DOI: 10.1267/ahc.23-00068] [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: 10/31/2023] [Accepted: 01/22/2024] [Indexed: 03/12/2024] Open
Abstract
We aimed to investigate the effects of short-term corticosteroid administration after anterior cruciate ligament (ACL) reconstruction on marrow adipose tissue (MAT) and trabecular bone mass, as well as to examine whether treadmill exercise can mitigate MAT increase and trabecular bone deterioration caused by corticosteroid. ACL-reconstructed rats were divided into groups: no intervention, daily treadmill exercise (60 min/day), administration of the steroidal drug dexamethasone (250 μg/kg on days 0-5, 7, and 9 post-operatively), or dexamethasone administration combined with treadmill exercise. Untreated rats were served as controls. At day 10 or 30 post-operatively, histological assessments were performed in the proximal tibial epiphysis. MAT accumulation and trabecular bone loss were observed after ACL reconstruction. Dexamethasone promoted MAT accumulation at day 10 post-operatively but did not affect the trabecular bone loss. The MAT accumulation caused by dexamethasone reversed within 21 days after discontinuation. Treadmill exercise did not influence the changes in the MAT and trabecular bone areas. Short-term corticosteroid administration after ACL reconstruction promoted MAT accumulation while not affecting trabecular bone area. The MAT accumulation resulting from corticosteroid administration was reversible after discontinuation. Treadmill exercise could not mitigate the accumulation of MAT caused by corticosteroid administration and did not affect trabecular bone area.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555–36, Higashi-Hiroshima, Hiroshima, Japan
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555–36, Higashi-Hiroshima, Hiroshima, Japan
| | - Junya Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555–36, Higashi-Hiroshima, Hiroshima, Japan
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Kaneguchi A, Yamaoka K, Ozawa J. Effects of Weight Bearing on Marrow Adipose Tissue and Trabecular Bone after Anterior Cruciate Ligament Reconstruction in the Rat Proximal Tibial Epiphysis. Acta Histochem Cytochem 2024; 57:15-24. [PMID: 38463204 PMCID: PMC10918432 DOI: 10.1267/ahc.23-00060] [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: 10/09/2023] [Accepted: 01/11/2024] [Indexed: 03/12/2024] Open
Abstract
The effects of mechanical unloading after anterior cruciate ligament (ACL) reconstruction on bone and marrow adipose tissue (MAT) are unclear. We investigated weight bearing effects on bone and MAT after ACL reconstruction. Rats underwent unilateral knee ACL transection and reconstruction, followed by hindlimb unloading (non-weight bearing), no intervention (low-weight bearing, the hindlimb standing time ratio (STR; operated/contralateral) during treadmill locomotion ranging from 0.55 to 0.91), or sustained morphine administration (moderate-weight bearing, STR ranging from 0.80 to 0.95). Untreated rats were used as controls. At 7 or 14 days after surgery, changes in trabecular bone and MAT in the proximal tibial were assessed histologically. Histological assessments at 7 or 14 days after surgery showed that ACL reconstruction without post-operative intervention did not significantly change trabecular bone and MAT areas. Hindlimb unloading after ACL reconstruction induced MAT accumulation with adipocyte hyperplasia and hypertrophy within 14 days, but did not significantly affect trabecular bone area. Increased weight bearing through morphine administration did not affect trabecular bone and MAT parameters. Our results suggest that early weight bearing after ACL reconstruction is important in reducing MAT accumulation, and that reduction in weight bearing alone is not sufficient to induce bone loss early after ACL reconstruction.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
| | - Junya Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
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Kaneguchi A, Hayakawa M, Shimoe A, Takahashi A, Yamaoka K, Ozawa J. The effects of weight bearing after ACL reconstruction on joint contracture in rats. Connect Tissue Res 2023; 64:543-554. [PMID: 37403736 DOI: 10.1080/03008207.2023.2232881] [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] [Received: 03/21/2023] [Revised: 05/29/2023] [Accepted: 06/26/2023] [Indexed: 07/06/2023]
Abstract
PURPOSE Joint contractures after anterior cruciate ligament (ACL) reconstruction are a serious problem. Given the uncertain effects of weight bearing after ACL reconstruction on contractures, this study was conducted to examine such effects. MATERIALS AND METHODS To control the amount of weight bearing, ACL-reconstructed rats were reared with either untreated (small weight bearing; weight bearing during locomotion was 54% of pre-surgery at minimum), hindlimb unloading (non-weight bearing), or sustained morphine administration (large weight bearing; weight bearing during locomotion was maintained at 80% or more of pre-surgery) conditions. Untreated rats were used as controls. Knee extension range of motions (ROMs) before (includes myogenic and arthrogenic factors) and after myotomy (includes arthrogenic factor only) and fibrotic reactions in the joint capsule were assessed 7 and 14 days post-surgery. RESULTS ACL reconstruction significantly reduced ROMs both before and after myotomy and induced fibrosis in the joint capsule accompanying upregulation of fibrosis-related genes (i.e., type I and III collagens and transforming growth factor-β1) at both time points. Morphine administration increased the ROM before myotomy, but not after myotomy 7 days post-surgery. Unloading after ACL reconstruction improved ROMs both before and after myotomy at both time points. In addition, unloading after ACL reconstruction attenuated fibrotic reactions in the joint capsule. CONCLUSIONS Our results suggest that morphine administration improves myogenic contractures in parallel with an increase in the amount of weight bearing. Unloading after ACL reconstruction is effective in reducing both myogenic and arthrogenic contractures.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Japan
| | - Momoka Hayakawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Japan
| | - Atsuhiro Shimoe
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Japan
| | - Akira Takahashi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Japan
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Japan
| | - Junya Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Japan
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Wegner E, Mickan T, Truffel S, Slotina E, Müller L, Wunderlich F, Harper A, Ritz U, Rommens PM, Gercek E, Drees P, Baranowski A. The effect of losartan on the development of post-traumatic joint stiffness in a rat model. Biomed Pharmacother 2023; 166:115291. [PMID: 37557010 DOI: 10.1016/j.biopha.2023.115291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 07/27/2023] [Accepted: 08/04/2023] [Indexed: 08/11/2023] Open
Abstract
Post-traumatic joint stiffness (PTJS) is accompanied by a multidimensional disturbance of joint architecture. Pharmacological approaches represent promising alternatives as the traumatic nature of current therapeutic standards may lead to PTJS' progression. Losartan is an auspicious candidate, as it has demonstrated an antifibrotic effect in other organs. Forty-eight Sprague Dawley rats were randomized into equally sized losartan or control groups. After a standardized knee trauma, the joint was immobilized for either 2 weeks (n = 16), 4 weeks (n = 16) or 4 weeks with re-mobilization for an additional 4 weeks (n = 16). Pharmacotherapy with losartan or placebo (30 mg/kg/day) was initiated on the day of trauma and continued for the entire course. Joint contracture was measured alongside histological and molecular biological assessments. There were no significant biomechanical changes in joint contracture over time, comparing short-term (2 weeks) with long-term losartan therapy (4 weeks). However, comparing the formation of PTJS with that of the control, there was a trend toward improvement of joint mobility of 10.5° (p 0.09) under the influence of losartan. During the re-mobilization phase, no significant effect of losartan on range of motion (ROM) was demonstrated. At a cellular level, losartan significantly reduced myofibroblast counts by up to 72 % (4 weeks, p ≤ 0.001) without effecting the capsular configuration. Differences in expression levels of profibrotic factors (TGF-β, CTGF, Il-6) were most pronounced at week 4. The antifibrotic properties of losartan are not prominent enough to completely prevent the development of PTJS after severe joint injury.
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Affiliation(s)
- Erik Wegner
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany
| | - Tim Mickan
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany
| | - Sebastian Truffel
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany
| | - Ekaterina Slotina
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany
| | - Lukas Müller
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany; Mainz Research School of Translational Biomedicine, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany
| | - Felix Wunderlich
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany
| | - Austin Harper
- St. George's University School of Medicine, True Blue, St. George, Grenada
| | - Ulrike Ritz
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany
| | - Pol M Rommens
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany
| | - Erol Gercek
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany
| | - Philipp Drees
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany
| | - Andreas Baranowski
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany.
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Zhou CX, Wang F, Zhou Y, Fang QZ, Zhang QB. Formation process of extension knee joint contracture following external immobilization in rats. World J Orthop 2023; 14:669-681. [PMID: 37744718 PMCID: PMC10514713 DOI: 10.5312/wjo.v14.i9.669] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/30/2023] [Accepted: 08/21/2023] [Indexed: 09/14/2023] Open
Abstract
BACKGROUND Current research lacks a model of knee extension contracture in rats.
AIM To elucidate the formation process of knee extension contracture.
METHODS We developed a rat model using an aluminum external fixator. Sixty male Sprague-Dawley rats with mature bones were divided into the control group (n = 6) and groups that had the left knee immobilized with an aluminum external fixator for 1, 2, and 3 d, and 1, 2, 3, 4, 6, and 8 wk (n = 6 in each group). The passive extension range of motion, histology, and expression of fibrosis-related proteins were compared between the control group and the immobilization groups.
RESULTS Myogenic contracture progressed very quickly during the initial 2 wk of immobilization. After 2 wk, the contracture gradually changed from myogenic to arthrogenic. The arthrogenic contracture progressed slowly during the 1st week, rapidly progressed until the 3rd week, and then showed a steady progression until the 4rd week. Histological analyses confirmed that the anterior joint capsule of the extended fixed knee became increasingly thicker over time. Correspondingly, the level of transforming growth factor beta 1 (TGF-β1) and phosphorylated mothers against decapentaplegic homolog 2 (p-Smad2) in the anterior joint capsule also increased with the immobilization time. Over time, the cross-sectional area of muscle fibers gradually decreased, while the amount of intermuscular collagen and TGF-β1, p-Smad2, and p-Smad3 was increased. Unexpectedly, the amount of intermuscular collagen and TGF-β1, p-Smad2, and p-Smad3 was decreased during the late stage of immobilization (6-8 wk). The myogenic contracture was stabilized after 2 wk of immobilization, whereas the arthrogenic contracture was stabilized after 3 wk of immobilization and completely stable in 4 wk.
CONCLUSION This rat model may be a useful tool to study the etiology of joint contracture and establish therapeutic approaches.
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Affiliation(s)
- Chen-Xu Zhou
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Feng Wang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Yun Zhou
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Qiao-Zhou Fang
- The Second Clinical Medicine College, Anhui Medical University, Hefei 230000, Anhui Province, China
| | - Quan-Bing Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
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Kaneguchi A, Shimoe A, Hayakawa M, Takahashi A, Yamaoka K, Ozawa J. The effects of weight bearing on muscle atrophy early after ACL reconstruction in rats. Tissue Cell 2023; 83:102148. [PMID: 37356383 DOI: 10.1016/j.tice.2023.102148] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 06/19/2023] [Accepted: 06/20/2023] [Indexed: 06/27/2023]
Abstract
We examined the effects of weight bearing after anterior cruciate ligament (ACL) reconstruction on muscle atrophy in rats. Rats were divided into the following groups: untreated control, ACL reconstruction (amount of weight bearing was small), ACL reconstruction plus hindlimb unloading (nonweight bearing), and ACL reconstruction plus morphine administration (amount of weight bearing was large) groups. At 7 or 14 days after surgery, atrophy of the rectus femoris and gastrocnemius was assessed. ACL reconstruction induced muscle atrophy in the rectus femoris and gastrocnemius. Unloading facilitated atrophy in the gastrocnemius but not in the rectus femoris. Morphine administration partially prevented atrophy in the gastrocnemius but not in the rectus femoris. After ACL reconstruction, the gene expression of insulin-like growth factor-1 (IGF-1), which is involved in protein synthesis, was downregulated in the gastrocnemius. Unloading decreased the gene expression of IGF-1 and increased the gene expression of atrogin-1, which is involved in protein breakdown, in the gastrocnemius. Morphine administration attenuated the downregulation of IGF-1. Atrophy of the gastrocnemius was more severe with a decrease in weight bearing, although the effect of weight bearing on rectus femoris atrophy was limited in rats. Early weight bearing is effective for reducing gastrocnemius muscle atrophy after ACL reconstruction.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan.
| | - Atsuhiro Shimoe
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
| | - Momoka Hayakawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
| | - Akira Takahashi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
| | - Junya Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
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Kaneguchi A, Takahashi A, Shimoe A, Hayakawa M, Yamaoka K, Ozawa J. The combined effects of treadmill exercise and steroid administration on anterior cruciate ligament reconstruction-induced joint contracture and muscle atrophy in rats. Steroids 2023; 192:109183. [PMID: 36690288 DOI: 10.1016/j.steroids.2023.109183] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/28/2022] [Accepted: 01/17/2023] [Indexed: 01/21/2023]
Abstract
Rehabilitation protocols to treat joint contracture and muscle atrophy following anterior cruciate ligament (ACL) reconstruction have not been established. In this study, we examined the combined effects of exercise therapy and steroid administration on joint contracture and muscle atrophy following ACL reconstruction. Rats received ACL transection and reconstructive surgery in one knee. After surgery, they were divided into four groups: no intervention, treadmill exercise (started from day three post-surgery, 12 m/min, 60 min/d, 6 d/week), treatment with the steroidal drug dexamethasone (250 μg/kg on days 0-5, 7, and 9 post-surgery), and dexamethasone treatment plus treadmill exercise. Age-matched untreated rats were used as controls. At day 10 or 30 post-surgery, we assessed ACL-reconstruction-induced joint contracture, joint capsule fibrosis, osteophyte formation, and muscle atrophy of the rectus femoris and gastrocnemius. Treadmill exercise after ACL reconstruction improved several indicators of muscle atrophy in both muscles, but it did not have positive effects on joint contracture. Dexamethasone treatment after ACL reconstruction improved joint contracture and joint capsule fibrosis at both timepoints and partially attenuated osteophyte formation at day 10 post-surgery, but delayed recovery from atrophy of the rectus femoris at day 30 post-surgery. The two treatments combined improved both joint contracture and atrophy of the rectus femoris and gastrocnemius. Exercise therapy combined with steroid administration may therefore be a novel therapeutic strategy for joint contracture and muscle atrophy following ACL reconstruction.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima 739-2695, Japan.
| | - Akira Takahashi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima 739-2695, Japan
| | - Atsuhiro Shimoe
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima 739-2695, Japan
| | - Momoka Hayakawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima 739-2695, Japan
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima 739-2695, Japan
| | - Junya Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima 739-2695, Japan
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Kaneguchi A, Ozawa J, Minamimoto K, Yamaoka K. The temporal and spatial effects of reconstructive surgery on the atrophy of hindlimb muscles in anterior cruciate ligament transected rats. Physiol Res 2023; 72:99-109. [PMID: 36545871 PMCID: PMC10069818 DOI: 10.33549/physiolres.934909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/24/2023] Open
Abstract
After anterior cruciate ligament (ACL) injury, a decrease in muscle strength associated with muscle atrophy is frequently observed. The temporal and spatial effects of reconstructive surgery on muscle atrophy have not been examined in detail. This study aimed to 1) reveal the short and mid-term effects of reconstructive surgery on muscle atrophy, and 2) investigate the differences in the degree of atrophy after ACL reconstruction in the hindlimb muscles. ACL transection with or without reconstructive surgery was performed unilaterally on the knees of rats. Untreated rats were used as controls. At one or four weeks post-surgery, the relative muscle wet weights (wet weight/body weight) of the hindlimb muscles were calculated to assess atrophy. At one week post-surgery, muscle atrophy was induced by ACL transection and further aggravated by reconstructive surgery. Reconstructive surgery facilitated recovery from muscle atrophy in some muscles compared with those without reconstructive surgery (ACL transection alone) at four weeks post-surgery. Muscle atrophy after ACL reconstruction was greater in the rectus femoris and plantar flexors than in the semitendinosus and plantar extensors at one week post-surgery. These results indicate that reconstructive surgery exacerbates muscle atrophy in the first week post-surgery, while facilitating recovery between the first and fourth week post-surgery. After reconstructive surgery, muscle atrophy was observed not only in the quadriceps and hamstrings, but also in the lower leg muscles, suggesting the need for muscle strengthening interventions for the lower leg muscles as well as the quadriceps and hamstrings.
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Affiliation(s)
- A Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Hiroshima, Japan.
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Kaneguchi A, Yamaoka K, Ozawa J. The effects of the amount of weight bearing on articular cartilage early after ACL reconstruction in rats. Connect Tissue Res 2023; 64:186-204. [PMID: 36334016 DOI: 10.1080/03008207.2022.2141627] [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: 11/06/2022]
Abstract
PURPOSE Osteoarthritis that develops after anterior cruciate ligament (ACL) reconstruction is a critical issue. We examined the effects of the amount of weight bearing early after ACL reconstruction on articular cartilage. MATERIALS AND METHODS Rats were divided into groups according to the treatment received: untreated control, ACL reconstruction (ACLR), ACL reconstruction plus hindlimb unloading (ACLR + HU), and ACL reconstruction plus morphine administration (ACLR + M). ACL reconstruction was performed on the right knee throughout the groups. To assess the amount of weight bearing, one-hindlimb standing time ratio (STR; operated side/contralateral side) during treadmill locomotion was evaluated during the experimental period. At day 7 or 14 post-surgery, cartilage degeneration of the medial tibial plateau was histologically assessed. RESULTS In the ACLR group, reduction in weight bearing characterized by significantly reduced STR was observed between day 1 and 7. Reduction in weight bearing was partially attenuated by morphine administration. Compared with the control group, the ACLR group exhibited an increased Mankin score that was accompanied by increased cyclooxygenase-2 expression in the anterior region. In the ACLR + HU group, Mankin scores were significantly higher in the middle and posterior regions, and cartilage thickness in these regions was significantly thinner than those in the ACLR group. In the ACLR + M group, although chondrocyte density in the anterior region was increased, all other parameters were not significantly different from those in the ACLR group. CONCLUSIONS Our results suggest that early weight bearing after ACL reconstruction is important to reduce cartilage degeneration.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Japan
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Japan
| | - Junya Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Japan
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The effects of immobilization duration on joint contracture formation after anterior cruciate ligament reconstruction in rats. Clin Biomech (Bristol, Avon) 2023; 103:105926. [PMID: 36868150 DOI: 10.1016/j.clinbiomech.2023.105926] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 02/17/2023] [Accepted: 02/21/2023] [Indexed: 03/05/2023]
Abstract
BACKGROUND Both myogenic and arthrogenic factors contribute to contracture formation after anterior cruciate ligament reconstruction surgery. However, effects of immobilization duration on myogenic and arthrogenic contractures after surgery are unknown. We examined the effects of immobilization duration on contracture formation. METHODS Rats were divided into groups according to treatment received: untreated control, knee immobilization, anterior cruciate ligament reconstruction, and anterior cruciate ligament reconstruction plus immobilization. Extension range of motion before and after myotomy as well as histomorphological knee changes were assessed two or four weeks after experiment commencement. Range of motion before myotomy mainly represents contractures due to myogenic factors. Range of motion after myotomy represents arthrogenic factors. FINDINGS Range of motion before and after myotomy was decreased in the immobilization, reconstruction, and reconstruction plus immobilization groups at both timepoints. In the reconstruction plus immobilization group, range of motion before and after myotomy was significantly smaller than in the immobilization and reconstruction groups. Shortening and thickening of the posterior joint capsule was induced in the immobilization and reconstruction groups. In the reconstruction plus immobilization group, capsule shortening was facilitated via adhesion formation, as compared to the immobilization and reconstruction groups. INTERPRETATION Our results indicate that immobilization after anterior cruciate ligament reconstruction surgery facilitates contracture formation via exacerbation of both myogenic and arthrogenic contractures within two weeks. Capsule shortening would be one of the main mechanisms for severe arthrogenic contracture observed in the reconstruction plus immobilization group. Periods of joint immobilization after surgery should be minimized to reduce contracture.
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Kaneguchi A, Yamaoka K, Ozawa J. Effects of joint immobilization and treadmill exercise on marrow adipose tissue and trabecular bone after anterior cruciate ligament reconstruction in the rat proximal tibial epiphysis. Acta Histochem 2023; 125:152012. [PMID: 36773546 DOI: 10.1016/j.acthis.2023.152012] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 02/01/2023] [Accepted: 02/03/2023] [Indexed: 02/11/2023]
Abstract
Marrow adipose tissue (MAT) adversely affects bone metabolism under certain conditions. Although mechanical stress is an important factor in regulating MAT and bone mass, how stress from different rehabilitation protocols after anterior cruciate ligament (ACL) reconstruction affects trabecular bone and MAT is unclear. We aimed to examine the effects of joint immobilization and treadmill exercise on trabecular bone and MAT after ACL reconstruction. Rats received unilateral knee ACL transection and reconstruction surgery. After surgery, rats were reared without intervention, with joint immobilization, or with treadmill exercise (12 m/min, 60 min/day, six days/week), with untreated rats as controls. At two or four weeks after starting experiments, we examined histological changes in trabecular bone and MAT in the proximal tibial epiphysis. After ACL reconstruction, there were no significant changes in trabecular bone area and MAT area at both time points. Joint immobilization after ACL reconstruction resulted in reduced trabecular bone area and MAT accumulation due to adipocyte hyperplasia and hypertrophy within four weeks. Treadmill exercise after ACL reconstruction did not affect any parameters in trabecular bone and MAT. We detected a moderate negative correlation between trabecular bone area and MAT area. Therefore, MAT accumulation induced by joint immobilization may contribute, at least in part, to reducing trabecular bone area. To minimize trabecular bone loss and MAT accumulation, joint immobilization after ACL reconstruction should be minimized. Exercise after ACL reconstruction did not alter trabecular bone and MAT.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan.
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
| | - Junya Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
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Kaneguchi A, Ozawa J, Yamaoka K. Effects of Joint Immobilization and Treadmill Exercise on Articular Cartilage After ACL Reconstruction in Rats. Orthop J Sports Med 2022; 10:23259671221123543. [PMID: 36276424 PMCID: PMC9580101 DOI: 10.1177/23259671221123543] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 07/06/2022] [Indexed: 11/06/2022] Open
Abstract
Background: The development of osteoarthritis after anterior cruciate ligament (ACL) reconstruction (ACLR) is an important issue. However, the appropriate rehabilitation protocol to prevent cartilage degeneration due to postoperative osteoarthritis is unclear. Purpose: To examine the effects of joint immobilization and treadmill exercise on articular cartilage after ACLR. Study Design: Controlled laboratory study. Methods: A total of 55 rats received unilateral knee ACL transection and reconstruction surgery using tail tendon autografts. After surgery, rats were reared without intervention, with joint immobilization, or with daily treadmill exercise (12 m/minute, 60 minutes/day, 6 days/week). Treadmill exercise was initiated at 3 or 14 days postoperatively. After 2 weeks of immobilization, the fixation device was removed from some of the immobilized rats, and the knee was allowed to move freely for 2 weeks. Untreated, age-matched rats (n = 8) were used as controls. At 2 or 4 weeks after starting the experiment, cartilage degeneration in the medial tibial plateau was histologically assessed using a modified Mankin score, cartilage thickness, chondrocyte density, and immunohistochemistry for cyclooxygenase-2 (COX-2) in the anterior, middle, and posterior regions. Results: After ACLR, cartilage degeneration in the anterior region characterized by increased Mankin score, accompanied with increased COX-2 expression, was detected. Joint immobilization after ACLR facilitated cartilage degeneration, which is detected by histological changes such as reductions in cartilage thickness, chondrocyte density, and high Mankin scores. Enhanced COX-2 expression in all degenerated cartilage regions was also detected. It was found that 2 weeks of remobilization could not restore cartilage degeneration induced by 2 weeks of immobilization after ACLR. Treadmill exercise after ACLR did not affect most articular cartilage parameters, regardless of the timing of exercise. Conclusion: Our results indicated that (1) immobilization after ACLR accelerates cartilage degeneration, even when applied only for 2 weeks, and (2) mild exercise during early phases after ACLR does not facilitate cartilage degeneration. Clinical Relevance: To reduce cartilage degeneration, periods of joint immobilization after ACLR should be minimized. Mild exercise during the early phases after ACLR will not negatively affect articular cartilage.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan
| | - Junya Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan.,Junya Ozawa, PT, PhD, Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, 739-2695, Japan ()
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan
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Conflicting time-dependent effects of treadmill exercise on joint contracture after anterior cruciate ligament reconstruction in rats. Tissue Cell 2022; 77:101861. [DOI: 10.1016/j.tice.2022.101861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 06/21/2022] [Accepted: 06/21/2022] [Indexed: 11/21/2022]
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Kaneguchi A, Ozawa J, Minamimoto K, Yamaoka K. Low-level laser therapy attenuates arthrogenic contracture induced by anterior cruciate ligament reconstruction surgery in rats. Physiol Res 2022; 71:389-399. [PMID: 35616040 DOI: 10.33549/physiolres.934796] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Therapeutic approaches to treat joint contracture after anterior cruciate ligament (ACL) reconstruction have not been established. Arthrofibrosis accompanied by joint inflammation following ACL reconstruction is a major cause of arthrogenic contracture. In this study, we examined whether anti-inflammatory treatment using low-level laser therapy (LLLT) can prevent ACL reconstruction-induced arthrogenic contracture. Rats underwent ACL transection and reconstruction surgery in their right knees. Unoperated left knees were used as controls. After surgery, rats were reared with or without daily LLLT (wavelength: 830 nm; power output: 150 mW; power density: 5 W/cm2; for 120 s/day). We assessed the passive extension range of motion (ROM) after myotomy at one and two weeks post-surgery; the reduction in ROM represents the severity of arthrogenic contracture. ROM was markedly decreased by ACL reconstruction at both time points; however, LLLT partially attenuated the decrease in ROM. One week after ACL reconstruction, the gene expression of the proinflammatory cytokine interleukin-1beta in the joint capsule was significantly upregulated, and this upregulation was significantly attenuated by LLLT. Fibrotic changes in the joint capsule, including upregulation of collagen type I and III genes, shortening of the synovium, and thickening were caused by ACL reconstruction and seen at both time points. LLLT attenuated these fibrotic changes as well. Our results indicate that LLLT after ACL reconstruction could attenuate the formation of arthrogenic contracture through inhibition of inflammation and fibrosis in the joint capsule. Thus, LLLT may become a novel therapeutic approach for ACL reconstruction-induced joint contracture.
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Affiliation(s)
- A Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Hiroshima, Japan.
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Marrow adipose tissue accumulation and dysgenesis of the trabecular bone after anterior cruciate ligament transection and reconstruction in the rat proximal tibial epiphysis. Acta Histochem 2022; 124:151891. [PMID: 35367815 DOI: 10.1016/j.acthis.2022.151891] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 03/07/2022] [Accepted: 03/24/2022] [Indexed: 11/23/2022]
Abstract
The accumulation of marrow adipose tissue (MAT) is frequently associated with bone loss. Although anterior cruciate ligament (ACL) injury induces bone loss, MAT accumulation after ACL injury has not been evaluated. In addition, no information about changes in MAT after ACL reconstruction is available. In this study, we aimed to examine (1) the effects of ACL transection on the amounts of trabecular bone and MAT present, and (2) whether ACL reconstruction inhibits the changes in the trabecular bone and MAT that are induced by ACL transection. ACL transection alone or with immediate reconstruction was performed on the right knees of rats. Untreated left knees were used as controls. Histomorphological changes in the trabecular bone and MAT in the proximal tibial epiphysis were examined prior to surgery and at one, four, and 12 weeks postsurgery. The trabecular bone area on the untreated side increased in a time-dependent manner. However, after ACL transection, the trabecular bone area did not increase during the experimental period, indicating dysgenesis of the bone (bone loss). Dysgenesis of the trabecular bone after ACL transection was attenuated by ACL reconstruction. MAT accumulation due to adipocyte hyperplasia and hypertrophy had been induced by ACL transection by four weeks postsurgery. This ACL transection-induced MAT accumulation was not prevented by ACL reconstruction. Based on these results, we conclude that (1) dysgenesis of the bone in the proximal tibia following ACL transection is accompanied by MAT accumulation, and (2) ACL reconstruction attenuates dysgenesis of the trabecular bone but cannot prevent MAT accumulation.
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Bilateral muscle atrophy after anterior cruciate ligament reconstruction in rats: Protective effects of anti-inflammatory drug celecoxib. Knee 2022; 35:201-212. [PMID: 35381572 DOI: 10.1016/j.knee.2022.03.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 02/17/2022] [Accepted: 03/21/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND Muscle atrophy after anterior cruciate ligament (ACL) reconstruction occurs bilaterally and contributes to a decrease in muscle strength. However, effective treatment strategies for ACL reconstruction-induced muscle atrophy have not been established. We examined the effects of anti-inflammatory drug on muscle atrophy after ACL reconstruction. MATERIALS AND METHODS Rats were divided into groups according to treatment received: untreated control (n = 4), arthrotomy (n = 6), ACL transection (n = 7), ACL reconstruction (n = 8), and ACL reconstruction plus anti-inflammatory drug celecoxib (CBX; 50 mg/kg/day) administration (n = 8). At one-week post-surgery, the muscle fiber cross-sectional area (CSA) in the rectus femoris (RF) and semitendinosus (ST) was measured to assess muscle atrophy. In addition, we examined joint swelling and serum C‑reactive protein (CRP) levels to assess local and systemic inflammation, respectively. RESULTS Each additional procedure (i.e., arthrotomy, ACL transection, and ACL reconstruction) gradually decreased the muscle fiber CSAs in the RF and ST on both operated and contralateral sides. The degree of muscle fiber atrophy on the operated side was larger than that detected on the contralateral side. Moreover, ACL reconstruction induced joint swelling on the operated side and tended to increase serum CRP levels. CBX lessened the RF atrophy on both sides and was associated with less joint swelling and a smaller increase CRP level; however, it did not affect ST atrophy on either side. CONCLUSIONS Anti-inflammatory treatments after ACL reconstruction may be effective in lessening muscle atrophy in the quadriceps, but not in the hamstrings.
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Kaneguchi A, Ozawa J, Minamimoto K, Yamaoka K. Effects of Each Phase of Anterior Cruciate Ligament Reconstruction Surgery on Joint Contracture in Rats. J INVEST SURG 2021; 35:984-995. [PMID: 34620030 DOI: 10.1080/08941939.2021.1985193] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Although anterior cruciate ligament reconstruction surgery is known to cause joint contracture, the mechanisms of this process are unknown. We aimed to assess the effects of transection of this ligament and each phase of reconstruction surgery on contracture formation. MATERIALS AND METHODS Rats were divided into groups according to treatment received: sham (arthrotomy), ligament transection, ligament transection plus bone drilling, and ligament reconstruction. Surgery was performed on the right knee. Untreated left knees in the sham group were used as controls. RESULTS At 7 and 28 d post-surgery, range of motion before myotomy, mainly representing myogenic contracture, was restricted in the sham and ligament transection groups, and more so in the bone drilling and reconstruction groups. Restricted range of motion after myotomy, representing arthrogenic contracture, was detected at both timepoints in the bone drilling and reconstruction groups, but not in the sham or ligament transection groups. At 3 d post-surgery, although a large blood clot was observed in all three treatment groups, only the bone drilling and reconstruction groups showed significant joint swelling. At 7 d post-surgery, inflammatory-cell infiltration into the joint capsule was most apparent in the bone drilling and reconstruction groups, and joint capsule fibrosis was also most apparent in these groups at 7 and 28 d post-surgery. CONCLUSIONS Our results suggest that (1) myogenic contracture after anterior cruciate ligament reconstruction is caused by arthrotomy and aggravated by bone drilling, and (2) arthrogenic contracture is mostly due to bone drilling, which triggers an inflammation-fibrosis cascade.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan
| | - Junya Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan
| | - Kengo Minamimoto
- Major in Medical Engineering and Technology, Graduate School of Medical Technology and Health Welfare Sciences, Hiroshima International University, Hiroshima, Japan
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan
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Effect of Radial Extracorporeal Shock Wave Combined With Ultrashort Wave Diathermy on Fibrosis and Contracture of Muscle. Am J Phys Med Rehabil 2020; 100:643-650. [DOI: 10.1097/phm.0000000000001599] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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