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Santana ÉTN, da Cunha Machado S, Brandão Lima VN, DeSantana Filho VJ, Dos Santos Maciel LY, de Farias Neto JP, Coutinho HDM, Martins N, Monteiro da Silva Júnior W, Quintans Júnior LJ. Comparison between exercise therapy and non-hydrolyzed collagen (UC-II) in functionality and quality of life in women with knee osteoarthritis : A randomized controlled clinical trial. Wien Klin Wochenschr 2023; 135:291-300. [PMID: 35612617 DOI: 10.1007/s00508-022-02037-8] [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: 09/27/2021] [Accepted: 04/21/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND Knee osteoarthritis (OA) is characterized by a progressive degeneration of cartilage and menisci, leading to pain and locomotor disability. Here, we aimed to assess the effect of an exercise protocol and the oral use of non-hydrolyzed collagen (UC-II) on the functionality and quality of life of women with knee OA. MATERIAL AND METHODS Individuals were divided into three groups (CG [control group]; MG [medication group]; EG [exercise group]). In the CG there was no intervention, while MG received an oral dose (1 capsule/day) of UC-II and the EG held 12 sessions of an exercise protocol. RESULTS In the functionality tests (6-min walk test, 6MWT and timed up and go test [TUG]) the EG (p < 0.001/p = 0.020) and MG (p = 0.010/p = 0.010) revealed a significant improvement when compared to the CG. In the analysis of quality of life by WOMAC, a significant improvement was found only in the EG (p = 0.030) when compared to the CG; the same happened in the stiffness domain (EG, p = 0.010), despite in the pain domain, both the EG (p < 0.001) and the MG (p = 0.060) were better than the CG. CONCLUSION Data obtained here reveal that an exercise protocol and UC-II have similar effects for functionality, despite exercise being superior in promoting the quality of life score.
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Roggio F, Petrigna L, Trovato B, Di Rosa M, Musumeci G. The Role of Lubricin, Irisin and Exercise in the Prevention and Treatment of Osteoarthritis. Int J Mol Sci 2023; 24:ijms24065126. [PMID: 36982198 PMCID: PMC10049370 DOI: 10.3390/ijms24065126] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 02/22/2023] [Accepted: 03/01/2023] [Indexed: 03/30/2023] Open
Abstract
Osteoarthritis is a chronic degenerative musculoskeletal disease that worsens with age and is defined by pathological alterations in joint components. All clinical treatment recommendations for osteoarthritis promote exercise, although precise molecular pathways are unclear. The purpose of this study was to critically analyze the research on lubricin and irisin and how they relate to healthy and diseased joint tissue. Our research focused specifically on exercise strategies and offered new perspectives for future potential osteoarthritis treatment plans. Although lubricin and irisin have only recently been discovered, there is evidence that they have an impact on cartilage homeostasis. A crucial component of cartilage lubrication and integrity, lubricin is a surface-active mucinous glycoprotein released by the synovial joint. Its expression increases with joint movement. In healthy joints, lubricin molecules cover the cartilage surface to lubricate the boundary of the joint and inhibit protein and cell attachment. Patients with joint trauma, inflammatory arthritis, or genetically mediated lubricin deficiency, who do not produce enough lubricin to protect the articular cartilage, develop arthropathy. Irisin, sometimes known as the "sports hormone", is a myokine secreted primarily by skeletal muscle. It is a physiologically active protein that can enter the circulation as an endocrine factor, and its synthesis and secretion are primarily triggered by exercise-induced muscle contraction. We searched PubMed, Web of Science, Google Scholar, and Scopus using the appropriate keywords to identify the most recent research. The studies considered advance our knowledge of the role that exercise plays in the fight against osteoarthritis, serve as a valuable resource, and support the advancement of osteoarthritis prevention and therapy.
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Affiliation(s)
- Federico Roggio
- Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Science, School of Medicine, University of Catania, Via S. Sofia 97, 95123 Catania, Italy
- Sport and Exercise Sciences Research Unit, Department of Psychology, Educational Science and Human Movement, University of Palermo, Via Giovanni Pascoli 6, 90144 Palermo, Italy
| | - Luca Petrigna
- Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Science, School of Medicine, University of Catania, Via S. Sofia 97, 95123 Catania, Italy
| | - Bruno Trovato
- Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Science, School of Medicine, University of Catania, Via S. Sofia 97, 95123 Catania, Italy
| | - Michelino Di Rosa
- Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Science, School of Medicine, University of Catania, Via S. Sofia 97, 95123 Catania, Italy
| | - Giuseppe Musumeci
- Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Science, School of Medicine, University of Catania, Via S. Sofia 97, 95123 Catania, Italy
- Research Center on Motor Activities (CRAM), University of Catania, Via S. Sofia 97, 95123 Catania, Italy
- Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
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Exploring the Potential Mechanism of Artemisinin and Its Derivatives in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:3976062. [PMID: 36590764 PMCID: PMC9800086 DOI: 10.1155/2022/3976062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/17/2022] [Accepted: 12/07/2022] [Indexed: 12/24/2022]
Abstract
Objective This study is aimed at predicting and contrasting the mechanisms of artemisinin (ARS), dihydroartemisinin (DHA), artesunate (ART), artemether (ARM), and arteether (ARE) in the treatment of osteoporosis (OP) using network pharmacology and molecular docking. Methods The targets of ARS, DHA, ART, ARM, and ARE were obtained from the SwissTargetPrediction. The targets related to OP were obtained from the TTD, DrugBank, Genecards, and DisGeNet databases. Then, the anti-OP targets of ARS, DHA, ART, ARM, and ARE were obtained and compared using the Venn diagram. Afterward, the protein-protein interaction (PPI) networks were built using the STRING database, and Cytoscape was used to select hub targets. Moreover, molecular docking validated the binding association between five molecules and hub targets. Finally, GO enrichment and KEGG pathway enrichment were conducted using the DAVID database. The common pathways of five molecules were analysed. Results A total of 28, 37, 36, 27, and 33 anti-OP targets of ARS, DHA, ART, ARM, and ARE were acquired. EGFR, EGFR, CASP3, MAPK8, and CASP3 act as the top 1 anti-OP targets of ARS, DHA, ART, ARM, and ARE, respectively. MAPK14 is the common target of five molecules. All five molecules can bind well with these hubs and common targets. Meanwhile, functional annotation showed that MAPK, Serotonergic synapse, AMPK, prolactin, and prolactin signaling pathways are the top 1 anti-OP pathway of ARS, DHA, ART, ARM, and ARE, respectively. IL-17 signaling pathway and prolactin signaling pathway are common anti-OP pathways of five molecules. Besides, GO enrichment showed five biological processes and three molecular functions are common anti-OP mechanisms of five molecules. Conclusion ARS, DHA, ART, ARM and ARE can treat OP through multi-targets and multi pathways, respectively. All five molecules can treat OP by targeting MAPK14 and acting on the IL-17 and prolactin signaling pathways.
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Eskelinen ASA, Florea C, Tanska P, Hung HK, Frank EH, Mikkonen S, Nieminen P, Julkunen P, Grodzinsky AJ, Korhonen RK. Cyclic loading regime considered beneficial does not protect injured and interleukin-1-inflamed cartilage from post-traumatic osteoarthritis. J Biomech 2022; 141:111181. [DOI: 10.1016/j.jbiomech.2022.111181] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 06/06/2022] [Accepted: 06/07/2022] [Indexed: 11/25/2022]
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Kong H, Wang XQ, Zhang XA. Exercise for Osteoarthritis: A Literature Review of Pathology and Mechanism. Front Aging Neurosci 2022; 14:854026. [PMID: 35592699 PMCID: PMC9110817 DOI: 10.3389/fnagi.2022.854026] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 03/11/2022] [Indexed: 12/14/2022] Open
Abstract
Osteoarthritis (OA) has a very high incidence worldwide and has become a very common joint disease in the elderly. Currently, the treatment methods for OA include surgery, drug therapy, and exercise therapy. In recent years, the treatment of certain diseases by exercise has received increasing research and attention. Proper exercise can improve the physiological function of various organs of the body. At present, the treatment of OA is usually symptomatic. Limited methods are available for the treatment of OA according to its pathogenesis, and effective intervention has not been developed to slow down the progress of OA from the molecular level. Only by clarifying the mechanism of exercise treatment of OA and the influence of different exercise intensities on OA patients can we choose the appropriate exercise prescription to prevent and treat OA. This review mainly expounds the mechanism that exercise alleviates the pathological changes of OA by affecting the degradation of the ECM, apoptosis, inflammatory response, autophagy, and changes of ncRNA, and summarizes the effects of different exercise types on OA patients. Finally, it is found that different exercise types, exercise intensity, exercise time and exercise frequency have different effects on OA patients. At the same time, suitable exercise prescriptions are recommended for OA patients.
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Affiliation(s)
- Hui Kong
- College of Kinesiology, Shenyang Sport University, Shenyang, China
| | - Xue-Qiang Wang
- Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, China
- Department of Rehabilitation Medicine, Shanghai Shangti Orthopedic Hospital, Shanghai, China
- *Correspondence: Xin-An Zhang,
| | - Xin-An Zhang
- College of Kinesiology, Shenyang Sport University, Shenyang, China
- Xue-Qiang Wang,
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Jang KM, Park YG, Choi WK, Chung YY, Kim KK, Lee JW, Lee SJ, Eom Y, Yang JH. Safety of a single intra-articular injection of LBSA0103 hyaluronic acid in patients with osteoarthritis of the knee: a multicenter, single-arm, prospective, cohort study. Curr Med Res Opin 2021; 37:1573-1580. [PMID: 34192989 DOI: 10.1080/03007995.2021.1950132] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE LBSA0103 is a recently developed high-molecular-weight, cross-linked, non-animal hyaluronic acid (HA). The safety of LBSA0103 has been investigated only in a limited number of patients, therefore this prospective study was designed. This study sought to assess the safety including injection-site reactions and adverse drug reactions after a single intra-articular injection of LBSA0103 in patients with osteoarthritis (OA) of the knee joint. METHODS This study was a multicenter, single-arm, prospective cohort study. After screening, eligible patients with OA of the knee joint (Kellgren-Lawrence grades I-III) were enrolled, received a single intra-articular HA (LBSA0103) injection, and were followed up for two weeks. Any adverse events including injection-site reactions and adverse drug reactions were evaluated by the investigators. RESULTS A total of 1949 subjects (2976 knee joints) was enrolled, all of whom received a single intra-articular injection of LBSA0103. Injection-site reactions occurred in 5.59% of enrolled subjects (109/1949), and the most frequently reported injection-site reaction was pain (4.87%), followed by swelling (1.03%). Most of the injection-site reactions were transient and resolved within 14 days without additional treatment. The incidence of adverse drug reactions other than injection-site reactions was 0.67% (13/1949). Most adverse events were of mild severity. No serious adverse events related to the study drug were reported. CONCLUSIONS A single intra-articular injection of LBSA0103 in patients with OA of the knee joint was safe, and no significant safety concerns were observed. As such, LBSA0103 could be safely applied as an intra-articular injection for the management of knee OA. TRIAL REGISTRATION The study was registered at ClinicalTrials.gov (identifier: NCT04369261).
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Affiliation(s)
- Ki-Mo Jang
- Department of Orthopedic Surgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Yong-Geun Park
- Department of Orthopedic Surgery, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - Won Kee Choi
- Department of Orthopedic Surgery, Daegu Catholic University Hospital, Daegu, Republic of Korea
| | - Young Yool Chung
- Department of Orthopedic Surgery, Kwangju Christian Hospital, Gwangju, Republic of Korea
| | - Kwang Kyoun Kim
- Department of Orthopedic Surgery, Konyang University Hospital, Konyang University College of Medicine, Daejeon, Republic of Korea
| | - Jang Woo Lee
- Department of Physical Medicine and Rehabilitation, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea
| | - Soong Joon Lee
- Department of Orthopedic Surgery, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Yunae Eom
- Life Sciences R&D, LG Chem, Ltd, Seoul, Republic of Korea
| | - Jae-Hyuk Yang
- Department of Orthopedic Surgery, Hanyang University Guri Hospital, Guri, Republic of Korea
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Jing Z, Wang C, Wen S, Jin Y, Meng Q, Liu Q, Wu J, Sun H, Liu M. Phosphocreatine Promotes Osteoblastic Activities in H 2O 2-Induced MC3T3-E1 Cells by Regulating SIRT1/FOXO1/PGC-1α Signaling Pathway. Curr Pharm Biotechnol 2021; 22:609-621. [PMID: 33198615 DOI: 10.2174/1389201021999201116160247] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 10/14/2020] [Accepted: 10/16/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Osteoporosis, characterized by bone loss, usually occurs with the increased bone resorption and decreased bone formation. H2O2-induced MC3T3-E1 cells are commonly used for the study of osteoblastic activities, which play a crucial role in bone formation. OBJECTIVE This study aimed to investigate the effects of Phosphocreatine (PCr) on the osteoblastic activities in H2O2-induced MC3T3-E1 cells and elaborate on the possible molecular mechanism. METHODS The Osteoprotegerin (OPG)/Receptor Activator of NF-κB Ligand (RANKL) ratio and osteogenic markers were detected to investigate the effects of PCr on osteoblastic activities, and the osteoblastic apoptosis was detected using Hochest staining. Moreover, oxidative stress, Adenosine Triphosphate (ATP) generation and the expression of Sirtuin 1 (SIRT1), Forkhead Box O 1 (FOXO1) and Peroxisome Proliferator-Activated Receptor Γ Coactivator-1α (PGC-1α) were also examined to uncover the possible molecular mechanism in H2O2-induced MC3T3-E1 cells. RESULT The results showed that PCr promoted the osteoblastic differentiation by increasing the expression levels of osteogenic markers of Alkaline Phosphatase (ALP) and Runt-related transcription factor 2 (Runx2), as well as increased the OPG/RANKL ratio and suppressed the osteoblastic apoptosis in H2O2-induced MC3T3-E1 cells. Moreover, treatment with PCr suppressed reactive oxygen species (ROS) over-generation and promoted the ATP production as well as increased the PGC-1α, FOXO1 and SIRT1 protein expression levels in H2O2-induced MC3T3-E1 cells. CONCLUSION PCr treatment could promote osteoblastic activities via suppressing oxidative stress and increasing the ATP generation in H2O2-induced MC3T3-E1 cells. In addition, the positive effects of PCr on osteoblasts might be regulated by SIRT1/FOXO1/ PGC-1α signaling pathway.
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Affiliation(s)
- Zheng Jing
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
| | - Changyuan Wang
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
| | - Shijie Wen
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
| | - Yue Jin
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
| | - Qiang Meng
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
| | - Qi Liu
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
| | - Jingjing Wu
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
| | - Huijun Sun
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
| | - Mozhen Liu
- Department of Orthopedics, First Affiliated Hospital, Dalian Medical University, Dalian, China
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Chuang LR, Yang WW, Chang PL, Chen VCF, Liu C, Shiang TY. Managing Vibration Training Safety by Using Knee Flexion Angle and Rating Perceived Exertion. SENSORS 2021; 21:s21041158. [PMID: 33562177 PMCID: PMC7915332 DOI: 10.3390/s21041158] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/25/2021] [Accepted: 02/03/2021] [Indexed: 01/08/2023]
Abstract
Whole-body vibration (WBV) is commonly applied in exercise and rehabilitation and its safety issues have been a major concern. Vibration measured using accelerometers can be used to further analyze the vibration transmissibility. Optimal bending angles and rating of perceived exertion (RPE) evaluations have not been sufficiently explored to mitigate the adverse effect. Therefore, the aims of this study were to investigate the effect of various knee flexion angles on the transmissibility to the head and knee, the RPE during WBV exposure, and the link between the transmissibility to the head and the RPE. Sixteen participants randomly performed static squats with knee flexion angles of 90, 110, 130, and 150 degrees on a WBV platform. Three accelerometers were fixed on the head, knee, and center of the vibration platform to provide data of platform-to-head and platform-to-knee transmissibilities. The results showed that the flexion angle of 110 degrees induced the lowest platform-to-head transmissibility and the lowest RPE (p < 0.01). A positive correlation between RPE and the platform-to-head transmissibility was observed. This study concluded that a knee flexion of about 110 degrees is most appropriate for reducing vibration transmissibility. The reported RPE could be used to reflect the vibration impact to the head.
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Affiliation(s)
- Long-Ren Chuang
- Department of Combat Sports and Chinese Martial Arts, Chinese Culture University, Taipei 11114, Taiwan; (L.-R.C.); (P.-L.C.)
| | - Wen-Wen Yang
- Department of Sports Medicine, China Medical University, Taichung 406040, Taiwan;
| | - Po-Ling Chang
- Department of Combat Sports and Chinese Martial Arts, Chinese Culture University, Taipei 11114, Taiwan; (L.-R.C.); (P.-L.C.)
| | | | - Chiang Liu
- Graduate Institute of Sports Equipment Technology, University of Taipei, Taipei 11153, Taiwan;
- Center for Sport Science and Technology, National Tsing Hua University, Hsinchu 300044, Taiwan
| | - Tzyy-Yuang Shiang
- Department of Athletic Performance, National Taiwan Normal University, Taipei 11677, Taiwan
- Correspondence: ; Tel.: +886-2-7749-6869
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Effects of mechanical stimuli on structure and organization of bone nanocomposites in rats with glucocorticoid-induced osteoporosis. Endocr Regul 2021; 55:42-51. [PMID: 33600670 DOI: 10.2478/enr-2021-0006] [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: 11/20/2022] Open
Abstract
Objective. Clinical use of glucocorticoids is a frequent cause of secondary osteoporosis, which reduces the mineral density of bones and results in pathological fractures. Mechanical stimulation as non-physiological high-frequency vibration with low acceleration prevents the loss of a crystalline component and stimulates the anabolic remodeling of the bone. The aim of the present research was to assess the impact of mechanical vibration on the bone structure in rats, which received glucocorticoids.Methods. Wistar rats were randomized into three groups: Vehicle control (Veh), Methylprednisolone sodium succinate (Mps), and Mps combined with whole-body vibration (WBV). Rats of Mps+WBV and Mps groups received 3 mg/kg/day of methylprednisolone every other day for 24 weeks and rats of Veh group received 0.9% saline (sodium chloride). The group of rats Mps+WBV was subjected to WBV for 30 minutes per day for five days a week with parameters 0.3 g and frequency 50 Hz. Relative amount of crystalline component and collagen in the bones was determined by X-ray diffraction (XRD) and calcium level - by atomic absorption spectroscopy. Bone tissue metabolism was assessed by determining the concentration of markers, in particular osteocalcin and Tartrate-resistant acid phosphatase (TRAP5b).Results. Glucocorticoids induced a considerable increase in the rats body mass (+13%) and decreased the content of mineral component in the femoral neck (-17%) in Mps group compared with Veh. The process of the bone metabolism was significantly accelerated, which is proven by an increased level of remodeling markers. It should be mentioned that WBV did not allow significant decrease in mineral component of the bone to 16th week of the experiment compared with Mps group, although these parameters did not achieve the indices in the Vehicle control group (-10%). Our investigation allows to suggest that mechanical high-frequency vibration of low intensity can partially inhibit the harmful consequences of glucocorticoids on bone structure in rats. Despite the positive impact of vibration on the bone tissue after Mps introduction in the 8th-16th week, this influence was not statistically reliable in the 24th week of the experiment.Conclusions. The results of our investigation on animal model indicate that non-physiological vertical mechanical vibrations are an effective means to prevent loss of a mineral bone component during treatment with glucocorticoids.
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Portier H, Benaitreau D, Pallu S. Does Physical Exercise Always Improve Bone Quality in Rats? Life (Basel) 2020; 10:life10100217. [PMID: 32977460 PMCID: PMC7598192 DOI: 10.3390/life10100217] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 09/17/2020] [Accepted: 09/18/2020] [Indexed: 12/17/2022] Open
Abstract
For decades, the osteogenic effect from different physical activities on bone in rodents remained uncertain. This literature review presents for the first time the effects on five exercise models (treadmill running, wheel running, swimming, resistance training and vibration modes) in three different experimental rat groups (males, females, osteopenic) on bone quality. The bone parameters presented are bone mineral density, micro-architectural and mechanical properties, and osteoblast/osteocyte and osteoclast parameters. This review shows that physical activities have a positive effect (65% of the results) on bone status, but we clearly observed a difference amongst the different protocols. Even if treadmill running is the most used protocol, the resistance training constitutes the first exercise model in term of osteogenic effects (87% of the whole results obtained on this model). The less osteogenic model is the vibration mode procedure (31%). It clearly appears that the gender plays a role on the bone response to swimming and wheel running exercises. Besides, we did not observe negative results in the osteopenic population with impact training, wheel running and vibration activities. Moreover, about osteoblast/osteocyte parameters, we conclude that high impact and resistance exercise (such jumps and tower climbing) seems to increase bone formation more than running or aerobic exercise. Among the different protocols, literature has shown that the treadmill running procedure mainly induces osteogenic effects on the viability of the osteocyte lineage in both males and females or ovariectomized rats; running in voluntary wheels contributes to a negative effect on bone metabolism in older male models; whole-body vertical vibration is not an osteogenic exercise in female and ovariectomized rats; whereas swimming provides controversial results in female models. For osteoclast parameters only, running in a voluntary wheel for old males, the treadmill running program at high intensity in ovariectomized rats, and the swimming program in a specific ovariectomy condition have detrimental consequences.
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Affiliation(s)
- Hugues Portier
- Laboratoire de Biologie Bioingénierie et Bioimagerie Ostéo-Articulaire (B3OA), Université Paris, UMR CNRS 7052, INSERM U1273, 10 Av de Verdun, 75010 Paris, France;
- Collegium Science & Technique, 2 allée du château, Université d’Orléans. 45100 Orléans, France;
- Correspondence: ; Tel.: +33-782-309-433
| | - Delphine Benaitreau
- Collegium Science & Technique, 2 allée du château, Université d’Orléans. 45100 Orléans, France;
| | - Stéphane Pallu
- Laboratoire de Biologie Bioingénierie et Bioimagerie Ostéo-Articulaire (B3OA), Université Paris, UMR CNRS 7052, INSERM U1273, 10 Av de Verdun, 75010 Paris, France;
- Collegium Science & Technique, 2 allée du château, Université d’Orléans. 45100 Orléans, France;
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Kärnsund S, Lo B, Bendtsen F, Holm J, Burisch J. Systematic review of the prevalence and development of osteoporosis or low bone mineral density and its risk factors in patients with inflammatory bowel disease. World J Gastroenterol 2020; 26:5362-5374. [PMID: 32994694 PMCID: PMC7504246 DOI: 10.3748/wjg.v26.i35.5362] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 05/04/2020] [Accepted: 08/21/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated disorders of the digestive tract. IBD is considered to be a risk factor for developing osteoporosis; however current literature on this matter is inconsistent.
AIM To assess prevalence and development of osteoporosis and low bone mineral density (BMD), and its risk factors, in IBD patients.
METHODS Systematic review of population-based studies. Studies were identified by electronic (January 2018) and manual searches (May 2018). Databases searched included EMBASE and PubMed and abstracts from 2014-2018 presented at the United European Gastroenterology Week, the European Crohn’s and Colitis Organisation congress, and Digestive Disease Week were screened. Studies were eligible for inclusion if they investigated either the prevalence of osteoporosis or osteopenia and/or risk factors for osteoporosis or low BMD in IBD patients. Studies on children under the age of 18 were excluded. Only population-based studies were included. All risk factors for osteoporosis and low BMD investigated in any included article were considered. Study quality and the possibility of bias were analysed using the Newcastle-Ottawa scale.
RESULTS Twelve studies including 3661 IBD patients and 12789 healthy controls were included. Prevalence of osteoporosis varied between 4%-9% in studies including both CD and UC patients; 2%-9% in studies including UC patients, and 7%-15% in studies including CD patients. Among healthy controls, prevalence of osteoporosis was 3% and 10% in two studies. CD diagnosis, lower body mass index (BMI), and lower body weight were risk factors associated with osteoporosis or low BMD. Findings regarding gender showed inconsistent results. CD patients had an increased risk for osteoporosis or low BMD over time, while UC patients did not. Increased age was associated with decreased BMD, and there was a positive association between weight and BMI and BMD over time. Great heterogeneity was found in the included studies in terms of study methodologies, definitions and the assessment of osteoporosis, and only a small number of population-based studies was available.
CONCLUSION This systematic review found a possible increase of prevalence of osteoporosis in CD cohorts when compared to UC and cohorts including both disease types. Lower weight and lower BMI were predictors of osteoporosis or low BMD in IBD patients. The results varied considerably between studies.
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Affiliation(s)
- Sofia Kärnsund
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| | - Bobby Lo
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| | - Flemming Bendtsen
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| | - Jakob Holm
- Department of Endocrinology, Copenhagen University Hospital Herlev, Herlev 4600, Denmark
| | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
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Tu J, Huang W, Zhang W, Mei J, Zhu C. The emerging role of lncRNAs in chondrocytes from osteoarthritis patients. Biomed Pharmacother 2020; 131:110642. [PMID: 32927251 DOI: 10.1016/j.biopha.2020.110642] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/07/2020] [Accepted: 08/16/2020] [Indexed: 02/07/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) play important roles in many physiological and pathological processes, including osteoarthritis (OA). Recent studies have demonstrated that lncRNAs are involved in the pathogenesis of OA by affecting various essential cellular features of chondrocytes, such as proliferation, apoptosis, inflammation, and degradation of the extracellular matrix (ECM). However, there are only a limited number of studies in this area, indicating that the role of lncRNAs in OA may have been overlooked. The aim of this literature review is to summarize the versatile roles and molecular mechanisms of lncRNAs in chondrocytes involved in OA. At the end of this article, the function of the lncRNA HOX transcript antisense RNA (HOTAIR) in chondrocytes in OA is highlighted. Because lncRNAs affect proliferation, apoptosis, inflammatory responses, and ECM degradation by chondrocytes in OA, they may serve as potential biomarkers or therapeutic targets for the diagnosis or treatment of OA. The specific role and related mechanisms of lncRNAs in OA warrants further investigation.
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Affiliation(s)
- Jiajie Tu
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, China.
| | - Wei Huang
- Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Weiwei Zhang
- Departments of Geriatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Jiawei Mei
- Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Chen Zhu
- Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
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13
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Ahmad V. Prospective of extracellular matrix and drug correlations in disease management. Asian J Pharm Sci 2020; 16:147-160. [PMID: 33995610 PMCID: PMC8105415 DOI: 10.1016/j.ajps.2020.06.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 04/20/2020] [Accepted: 06/22/2020] [Indexed: 12/30/2022] Open
Abstract
The extracellular matrix (ECM) comprises of many structural molecules that constitute the extracellular environment. ECM molecules are characterized by specific features like diversity, complexity and signaling, which are also results of improvement or development of disease mediated by some physiological changes. Several drugs have also been used to manage diseases and they have been reported to modulate ECM assembly, including physiological changes, beyond their primary targets and ECM metabolism. This review highlights the alteration of ECM environment for diseases and effect of different classes of drugs like nonsteroidal anti-inflammatory drugs, immune suppressant drug, steroids on ECM or its components. Thus, it is summarized from previously conducted researches that diseases can be managed by targeting specific components of ECM which are involved in the pathophysiology of diseases. Moreover, the drug delivery focused on targeting the ECM components also has the potential for the discovery of targeted and site specific release of drugs. Therefore, ECM or its components could be future targets for the development of new drugs for controlling various disease conditions including neurodegenerative diseases and cancers.
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Affiliation(s)
- Varish Ahmad
- Health Information Technology Department, Faculty of Applied Studies, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia
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14
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HIF-1α induces hypoxic apoptosis of MLO-Y4 osteocytes via JNK/caspase-3 pathway and the apoptotic-osteocyte-mediated osteoclastogenesis in vitro. Tissue Cell 2020; 67:101402. [PMID: 32835935 DOI: 10.1016/j.tice.2020.101402] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 06/25/2020] [Accepted: 06/26/2020] [Indexed: 02/07/2023]
Abstract
Apoptotic osteocytes were found in the hypoxic bone microenvironment in osteoporosis, osteotomy, orthodontic tooth movement and periodontitis, and played a key role in bone remolding and the differentiation of osteoclasts. Hypoxia inducible factor-1α(HIF-1α), as a transcription factor under hypoxic conditions, has been confirmed to participate in cell apoptosis. However, the effect of HIF-1α on osteocytes apoptosis and the osteocyte-mediated osteoclast formation remains elusive. Here, we hypothesized that HIF-1α was involved in osteocytes apoptosis. Our results showed that CoCl2 increased the MLO-Y4 cells apoptosis by upregulating the proapoptotic gene expression of caspase-3. Moreover, siRNA-mediated knockdown of HIF-1α decreased the phosphorylation by JNK and the activation of caspase-3 to inhibit the cell apoptosis in MLO-Y4. Furthermore, SP600125, an inhibitor of JNK, reversed CoCl2-induced the increased apoptosis of MLO-Y4 cells in term of reducing the expression of caspase-3. These findings revealed that HIF-1α served as a pro-apoptotic factor in the apoptosis of MLO-Y4 cells cultured with CoCl2, by activating the JNK/caspase-3 signaling pathway. Besides, the osteocyte-mediated osteoclastogenesis was reduced with the decline of the expression of HIF-1α and caspase-3 in MLO-Y4 cells. Our study provided an idea for a more comprehensive understanding of HIF-1α and the process of bone remodeling.
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15
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Effect of Whole-Body Vibration on the Functional Responses of the Patients with Knee Osteoarthritis by the Electromyographic Profile of the Vastus Lateralis Muscles during the Five-Repetition Chair Stand Test: A Randomized Crossover Trial. APPLIED SCIENCES-BASEL 2020. [DOI: 10.3390/app10124302] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Knee osteoarthritis (KOA) can cause functional disability. Neuromuscular function is relevant in the development and progression of KOA. It can be evaluated by the analysis of the surface electromyography (sEMG), which has an important role in the understanding of KOA. Whole-body vibration (WBV) is an intervention suggested to treat KOA. The objective of this work was to verify the effectiveness of WBV on the functionality of lower limbs by the electromyographic profile of the vastus lateralis (VL) muscles during the five-repetition chair stand test (5CST) in patients with KOA. This was a two-period crossover trial study (8-week washout). Nineteen patients with KOA were allocated to the group submitted to WBV (WBVG), with peak-to-peak displacement of 2.5 to 7.5 mm, frequency from 5 to 14 Hz, and acceleration peak from 0.12 to 2.95 g, or to the control group (0 Hz) (2 days per week for 5 weeks). The 5CST and the sEMG of the VL during 5CST were evaluated before and after the interventions. Results: Significant differences in 5CST were evident only in WBVG (p = 0.018), showing a decrease of the execution time. The sEMG profile showed no significative difference. Therefore, only 10 sessions of WBV with comfortable posture can bring about improvement in functionality of KOA patients without alteration of the muscle excitation.
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16
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Gao H, Peng L, Li C, Ji Q, Li P. Salidroside Alleviates Cartilage Degeneration Through NF-κB Pathway in Osteoarthritis Rats. DRUG DESIGN DEVELOPMENT AND THERAPY 2020; 14:1445-1454. [PMID: 32341638 PMCID: PMC7166061 DOI: 10.2147/dddt.s242862] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 02/20/2020] [Indexed: 12/13/2022]
Abstract
Introduction Osteoarthritis (OA) is the most common disease, which seriously affects the daily life of the elderly. Currently, no traditional or drug therapy has been shown to explicitly block the progression of OA. Salidroside (Sal) is a bioactive component of Rhodiola rosea, which has many beneficial effects on human health. However, the role and mechanism of Sal in OA have not been reported. Methods We established an anterior cruciate ligament transection (ACLT)-induced OA Rat model. The rats were divided into five groups (n = 10): Control group; ACLT group; ACLT + Sal (12.5 mg/kg) group; ACLT + Sal (25 mg/kg) group; ACLT + Sal (50 mg/kg) group. Results The study showed that Sal could significantly promote the proliferation of chondrocytes in OA rats induced by ACLT and restore the histological alteration of cartilage. Besides, Sal upregulated the levels of Collagen II and Aggrecan, and downregulated the level of MMP-13. Furthermore, Sal could reduce the number of CD4+IL-17+ cells and decrease the levels of IL-17, IKBα and p65, while elevating the number of CD4+IL-10+ cells and the level of IL-10. The decrease of IL-17 further inhibited the dissociation of IKBα to p65, thus reducing the release of TNF-α and VCAM-1. Taken together, Sal alleviates cartilage degeneration through promoting chondrocytes proliferation, inhibiting collagen fibrosis, and regulating inflammation and immune responses via NF-κB pathway in ACLT-induced OA Rats. Discussion Collectively, our study investigates the role and mechanism of Sal in OA, which lays a foundation for the application of Sal in OA.
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Affiliation(s)
- Hui Gao
- Department of Orthopaedics, Tinglin Hospital, Shanghai 201505, People's Republic of China
| | - Lu Peng
- Department of Orthopaedics, Hospital of Traditional Chinese Medicine, E'dong Healthcare Group, Huangshi 435000, People's Republic of China
| | - Chao Li
- Department of Orthopaedics, Tinglin Hospital, Shanghai 201505, People's Republic of China
| | - Qinlong Ji
- Department of Orthopaedics, Tinglin Hospital, Shanghai 201505, People's Republic of China
| | - Ping Li
- Department of Rehabilitation, Hanchuan People's Hospital, Hanchuan, 431600, People's Republic of China
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Xu G, Wang J, Ma L, Zhao X, Luo W, Jin Q. Local intra-articular injection of rapamycin inhibits NLRP3 activity and prevents osteoarthritis in mouse DMM models. Autoimmunity 2019; 52:168-175. [PMID: 31407595 DOI: 10.1080/08916934.2019.1643844] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
This study investigated the influence of autophagy on the expression of Collagen type II and light chain 3 (LC-3) in the articular cartilage of osteoarthritis (OA) models. The expression of OA associated biomarkers namely Matrix metalloproteinase (MMP-13), NOD-, LRR- and pyrin domain-containing 3 (NLRP3) induced by destabilizing the medial meniscus operation (DMM) were also investigated. A total of 60 C57BL/6 mice were divided into (1) control; (2) DMM2; (3) DMM8; (4) rapamycin 2 weeks; and (5) rapamycin 8 weeks groups. Saffranin O-Fast green staining, histomorphometry and immunohistochemical methods were used for analysis. In the DMM group, the expression of the OA biomarkers MMP-13, NLRP3 significantly increased, whilst Collagen II and LC-3B levels were significantly lower than other experimental groups. We hypothesized that NLRP3 inhibits autophagy activation and delays disease progression.
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Affiliation(s)
- Gang Xu
- The General Hospital of Ningxia Medical University, Ningxia Medical University , Yinchuan , PR China
| | - Jian Wang
- The General Hospital of Ningxia Medical University, Ningxia Medical University , Yinchuan , PR China
| | - Long Ma
- The General Hospital of Ningxia Medical University, Ningxia Medical University , Yinchuan , PR China.,Orthopedics Ward 3, The General Hospital of Ningxia Medical University , Yinchuan , PR China
| | - Xin Zhao
- The General Hospital of Ningxia Medical University, Ningxia Medical University , Yinchuan , PR China.,Orthopedics Ward 3, The General Hospital of Ningxia Medical University , Yinchuan , PR China
| | - Wen Luo
- The General Hospital of Ningxia Medical University, Ningxia Medical University , Yinchuan , PR China
| | - Qunhua Jin
- The General Hospital of Ningxia Medical University, Ningxia Medical University , Yinchuan , PR China.,Orthopedics Ward 3, The General Hospital of Ningxia Medical University , Yinchuan , PR China
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Thorson C, Galicia K, Burleson A, Bouchard O, Hoppensteadt D, Fareed J, Hopkinson W. Matrix Metalloproteinases and Their Inhibitors and Proteoglycan 4 in Patients Undergoing Total Joint Arthroplasty. Clin Appl Thromb Hemost 2019; 25:1076029619828113. [PMID: 30754994 PMCID: PMC6714937 DOI: 10.1177/1076029619828113] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Osteoarthritis, a degenerative disease of the joints, is the most common form of arthritis in the knee. Total joint arthoplasty is a commonly used treatment for joint degeneration and osteoarthritis, and due to these factors, TJA for hip and knee joints is projected to grow by 137% and 601% between 2005 and 2030. Matrix metalloproteases are enzymes found in the extracellular matrix that cleave matrix components. Normally MMPs are downregulated in tissues by Tissue Inhibitors of Metalloproteases, or TIMPs. The relative concentration of TIMPs also may denote some of the activity of the MMPs found in serum. Lubricin (proteoglycan 4) is a molecule found in the synovial fluid that protects joints by dissipating strain energy during locomotion. Lubricin synovial fluid concentration is also diminished in many patients with osteoarthritis, but not all. Given the importance of these three sets of molecules, our lab investigated the correlation between circulating lubricin, MMP levels and TIMPs levels. Blood plasma samples were obtained from de-identified subjects undergoing total joint arthroplasty at Loyola University Medical Center and the University of Utah. Normal blood plasma from pooled healthy individuals served as a control. We analyzed biomarker levels in plasma using ELISA. Our data show that MMP-1 and 9 were increased in TJA patients compared to normal controls, while MMP-2 and 13 were decreased. We also found decreased lubricin and tissue factor in surgical patients relative to controls. These data support the idea that lubricin is vital in protecting the synovial joint and that MMPs play a complex role in the destruction of the joint.
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Affiliation(s)
- Chase Thorson
- 1 Department of Pathology, Loyola University Medical Center, Maywood, IL, USA
| | - Kevin Galicia
- 1 Department of Pathology, Loyola University Medical Center, Maywood, IL, USA
| | - Andrew Burleson
- 2 Department of Orthopedics, Loyola University Medical Center, Maywood, IL, USA
| | - Olivia Bouchard
- 1 Department of Pathology, Loyola University Medical Center, Maywood, IL, USA
| | - Debra Hoppensteadt
- 1 Department of Pathology, Loyola University Medical Center, Maywood, IL, USA
| | - Jawed Fareed
- 1 Department of Pathology, Loyola University Medical Center, Maywood, IL, USA
| | - William Hopkinson
- 2 Department of Orthopedics, Loyola University Medical Center, Maywood, IL, USA
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19
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Mazor M, Best TM, Cesaro A, Lespessailles E, Toumi H. Osteoarthritis biomarker responses and cartilage adaptation to exercise: A review of animal and human models. Scand J Med Sci Sports 2019; 29:1072-1082. [DOI: 10.1111/sms.13435] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Revised: 03/29/2019] [Accepted: 04/04/2019] [Indexed: 12/20/2022]
Affiliation(s)
| | - Thomas M. Best
- Division of Sports Medicine, Department of Orthopedics, Health Sports Medicine Institute University of Miami Coral Gables Florida
| | | | - Eric Lespessailles
- University of Orléans Orléans France
- Service de Rhumatologie Centre Hospitalier Régional d'Orléans La Source France
| | - Hechmi Toumi
- University of Orléans Orléans France
- Service de Rhumatologie Centre Hospitalier Régional d'Orléans La Source France
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20
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Sun ZP, Wu SP, Liang CD, Zhao CX, Sun BY. The synovial fluid neuropeptide PACAP may act as a protective factor during disease progression of primary knee osteoarthritis and is increased following hyaluronic acid injection. Innate Immun 2019; 25:255-264. [PMID: 30935267 PMCID: PMC6830887 DOI: 10.1177/1753425919839125] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Revised: 02/25/2019] [Accepted: 02/28/2019] [Indexed: 11/15/2022] Open
Abstract
The correlation of serum and synovial fluid (SF) pituitary adenylate cyclase-activating polypeptide (PACAP) levels with disease progression of primary knee osteoarthritis (OA) was explored. Radiographic severity of OA was determined by Kellgren-Lawrence (K-L) grades. PACAP levels were measured by ELISA before treatment, and 4 and 8 wk following hyaluronic acid (HA) injection. Levels of IL-1β and MMP-3 were also detected. The numeric pain scale (NPS), revised Oxford Knee Score (OKS), and American Knee Society Score (AKSS) were employed to evaluate to symptomatic severity. Receiver-operating-characteristic (ROC) curve analysis was carried out to compare the diagnostic value of PACAP, IL-1β, and MMP-3 for the K-L grade. PACAP concentrations in SF but not serum were significantly lower in OA patients compared with controls. SF PACAP levels were negatively associated with K-L grades and higher NPS as well as worse AKSS and OKS. Further analysis demonstrated that PACAP concentration in SF was negatively correlated with expressions of IL-1β as well as MMP-3 and may act as a marker for radiographic progression along with MMP-3. Last, we found SF PACAP levels exhibited an incremental trend after HA injection. These findings confirmed the crucial role of PACAP deficiency in the development of primary knee OA.
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Affiliation(s)
- Zheng-Ping Sun
- Department of Orthopedics, Guangdong Province Second Hospital of
Traditional Chinese Medicine, Guangzhou, China
| | - Shao-Peng Wu
- Department of Orthopedics, Guangdong Province Second Hospital of
Traditional Chinese Medicine, Guangzhou, China
| | - Can-De Liang
- Department of Orthopedics, Guangdong Province Second Hospital of
Traditional Chinese Medicine, Guangzhou, China
| | - Chuan-Xi Zhao
- Department of Orthopedics, Guangdong Province Second Hospital of
Traditional Chinese Medicine, Guangzhou, China
| | - Bing-Yin Sun
- Department of Orthopedics, Shunde Hospital of Guangzhou
University of Chinese Medicine (ShunDe District Hospital of Chinese Medicine of
Foshan City), Foshan, China*The authors contributed equally to this work
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21
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de Lamas C, de Castro MJ, Gil-Campos M, Gil Á, Couce ML, Leis R. Effects of Dairy Product Consumption on Height and Bone Mineral Content in Children: A Systematic Review of Controlled Trials. Adv Nutr 2019; 10:S88-S96. [PMID: 31089738 PMCID: PMC6518138 DOI: 10.1093/advances/nmy096] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Revised: 09/11/2018] [Accepted: 10/25/2018] [Indexed: 12/25/2022] Open
Abstract
There is a physiological basis for the roles of selected nutrients, especially proteins, calcium, and vitamin D, in growth and development, which are at a maximum during the pediatric period. Milk and dairy products are particularly rich in this group of nutrients. The present systematic review summarizes the available evidence relating dairy product intake with linear growth and bone mineral content in childhood and adolescence. A search was conducted in the MEDLINE (via PubMed) and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included intervention-controlled clinical trials with dairy products in children from 1 January, 1926 to 30 June, 2018. The risk of bias for each study was assessed using the Cochrane methodology. The number of study participants, the type of study and doses, the major outcomes, and the key results of the 13 articles included in the review are reported. The present systematic review shows that supplementing the usual diet with dairy products significantly increases bone mineral content during childhood. However, the results regarding a possible relation between dairy product consumption and linear growth are inconclusive.
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Affiliation(s)
- Carmela de Lamas
- Department of Forensic Sciences, Pathological Anatomy, Gynecology and Obstetrics and Pediatrics, University of Santiago de Compostela, Santiago de Compostela, Spain
- Pediatric Metabolism and Research Unit, Department of Pediatrics, Reina Sofia University Hospital, IMIBIC, University of Cordoba, Cordoba, Spain
- CIBEROBN, Madrid, Spain
- Department of Pediatrics, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
- IDIS-Sanitary Research Institute of Santiago de Compostela, Santiago de Compostela, Spain
| | - María José de Castro
- Department of Pediatrics, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
- IDIS-Sanitary Research Institute of Santiago de Compostela, Santiago de Compostela, Spain
- CIBERER, Madrid, Spain
| | - Mercedes Gil-Campos
- Pediatric Metabolism and Research Unit, Department of Pediatrics, Reina Sofia University Hospital, IMIBIC, University of Cordoba, Cordoba, Spain
- CIBEROBN, Madrid, Spain
| | - Ángel Gil
- CIBEROBN, Madrid, Spain
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada, Spain
- Institute of Nutrition and Food Technology “José Mataix,” Biomedical Research Center, University of Granada, Granada, Spain
| | - María Luz Couce
- Department of Forensic Sciences, Pathological Anatomy, Gynecology and Obstetrics and Pediatrics, University of Santiago de Compostela, Santiago de Compostela, Spain
- Department of Pediatrics, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
- IDIS-Sanitary Research Institute of Santiago de Compostela, Santiago de Compostela, Spain
- CIBERER, Madrid, Spain
| | - Rosaura Leis
- Department of Forensic Sciences, Pathological Anatomy, Gynecology and Obstetrics and Pediatrics, University of Santiago de Compostela, Santiago de Compostela, Spain
- CIBEROBN, Madrid, Spain
- Department of Pediatrics, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
- IDIS-Sanitary Research Institute of Santiago de Compostela, Santiago de Compostela, Spain
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22
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Lee G. Whole-Body Vibration in Horizontal Direction for Stroke Rehabilitation: A Randomized Controlled Trial. Med Sci Monit 2019; 25:1621-1628. [PMID: 30825302 PMCID: PMC6408868 DOI: 10.12659/msm.912589] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background As most of the existing whole-body vibration (WBV) training programs provide vertical or rotatory vibration, studies on the effects of horizontal vibration have rarely been reported. The present study was conducted to investigate the effect of WBV in the horizontal direction on balance and gait ability in chronic stroke survivors. Material/Methods This study was designed as a randomized controlled trial. Twenty-one stroke survivors were randomly allocated into 2 groups (whole-body vibration group [n=9] and control group [n=12]). In the WBV group, WBV training in the horizontal direction was conducted for 6 weeks, and a conventional rehabilitation for 30 min, 3 days per week for a 6-week period, was conducted in both the WBV and control groups. Outcome variables included the static balance and gait ability measured before training and after 6 weeks. Results On comparing the outcome variables before and after training in the WBV group, significant differences were observed in the cadence and single support time of gait ability. However, there were no significant differences in other variables, including velocity, step length, stride length, and double support time. In addition, after training, no significant differences in all variables were observed between the 2 groups. Conclusions The results of this study suggest that WBV training in the horizontal direction has few positive effects on balance and gait function in chronic stroke survivors. However, further investigation is needed to confirm this.
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Affiliation(s)
- GyuChang Lee
- Department of Physical Therapy, Kyungnam University, Changwon, South Korea
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23
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Castrogiovanni P, Di Rosa M, Ravalli S, Castorina A, Guglielmino C, Imbesi R, Vecchio M, Drago F, Szychlinska MA, Musumeci G. Moderate Physical Activity as a Prevention Method for Knee Osteoarthritis and the Role of Synoviocytes as Biological Key. Int J Mol Sci 2019; 20:ijms20030511. [PMID: 30691048 PMCID: PMC6387266 DOI: 10.3390/ijms20030511] [Citation(s) in RCA: 121] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2018] [Revised: 01/22/2019] [Accepted: 01/23/2019] [Indexed: 12/22/2022] Open
Abstract
The purpose of this study was to investigate the influence of moderate physical activity (MPA) on the expression of osteoarthritis (OA)-related (IL-1β, IL-6, TNF-α, MMP-13) and anti-inflammatory and chondroprotective (IL-4, IL-10, lubricin) biomarkers in the synovium of an OA-induced rat model. A total of 32 rats were divided into four groups: Control rats (Group 1); rats performing MPA (Group 2); anterior cruciate ligament transection (ACLT)-rats with OA (Group 3); and, ACLT-rats performing MPA (Group 4). Analyses were performed using Hematoxylin & Eosin (H&E) staining, histomorphometry and immunohistochemistry. In Group 3, OA biomarkers were significantly increased, whereas, IL-4, IL-10, and lubricin were significantly lower than in the other experimental groups. We hypothesize that MPA might partake in rescuing type B synoviocyte dysfunction at the early stages of OA, delaying the progression of the disease.
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Affiliation(s)
- Paola Castrogiovanni
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia n°87, 95124 Catania, Italy.
| | - Michelino Di Rosa
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia n°87, 95124 Catania, Italy.
| | - Silvia Ravalli
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia n°87, 95124 Catania, Italy.
| | - Alessandro Castorina
- School of Life Sciences, Faculty of Science, University of Technology Sydney, P.O. Box 123, Broadway, Sydney, NSW 2007, Australia.
- Discipline of Anatomy and Histology, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
| | - Claudia Guglielmino
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia n°87, 95124 Catania, Italy.
| | - Rosa Imbesi
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia n°87, 95124 Catania, Italy.
| | - Michele Vecchio
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, via S. Sofia 67, 95123 Catania, Italy.
| | - Filippo Drago
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, via S. Sofia 67, 95123 Catania, Italy.
| | - Marta Anna Szychlinska
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia n°87, 95124 Catania, Italy.
| | - Giuseppe Musumeci
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia n°87, 95124 Catania, Italy.
- School of the Sport of the Italian National Olympic Committee "CONI" Sicily, Via Emanuele Notarbartolo, 90141 Palermo, Italy.
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Parween R, Shriram D, Mohan RE, Lee YHD, Subburaj K. Methods for evaluating effects of unloader knee braces on joint health: a review. Biomed Eng Lett 2019; 9:153-168. [PMID: 31168421 DOI: 10.1007/s13534-019-00094-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 12/13/2018] [Accepted: 01/08/2019] [Indexed: 02/01/2023] Open
Abstract
The paper aims to provide a state-of-the-art review of methods for evaluating the effectiveness and effect of unloader knee braces on the knee joint and discuss their limitations and future directions. Unloader braces are prescribed as a non-pharmacological conservative treatment option for patients with medial knee osteoarthritis to provide relief in terms of pain reduction, returning to regular physical activities, and enhancing the quality of life. Methods used to evaluate and monitor the effectiveness of these devices on patients' health are categorized into three broad categories (perception-, biochemical-, and morphology-based), depending upon the process and tools used. The main focus of these methods is on the short-term clinical outcome (pain or unloading efficiency). There is a significant technical, research, and clinical literature gap in understanding the short- and long-term consequences of these braces on the tissues in the knee joint, including the cartilage and ligaments. Future research directions may complement existing methods with advanced quantitative imaging (morphological, biochemical, and molecular) and numerical simulation are discussed as they offer potential in assessing long-term and post-bracing effects on the knee joint.
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Affiliation(s)
- Rizuwana Parween
- 1Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Road, Singapore, 487372 Singapore
| | - Duraisamy Shriram
- 1Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Road, Singapore, 487372 Singapore
| | - Rajesh Elara Mohan
- 1Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Road, Singapore, 487372 Singapore
| | - Yee Han Dave Lee
- 2Changi General Hospital, 2 Simei Street 3, Singapore, 529889 Singapore
| | - Karupppasamy Subburaj
- 1Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Road, Singapore, 487372 Singapore
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The " Journal of Functional Morphology and Kinesiology" Journal Club Series: Highlights on Recent Papers in Exercise and Osteoarthritis. J Funct Morphol Kinesiol 2019; 4:jfmk4010007. [PMID: 33467322 PMCID: PMC7739403 DOI: 10.3390/jfmk4010007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 01/17/2019] [Indexed: 12/20/2022] Open
Abstract
We are glad to introduce the eleventh Journal Club. This edition is focused on several relevant studies published in the last years in the field of exercise and osteoarthritis, chosen by our Editorial Board members and their colleagues. We hope to stimulate your curiosity in this field and to share with you the passion for sport seen also from the scientific point of view. The Editorial Board members wish you an inspiring lecture.
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Zhang Y, Chai Y, Pan X, Shen H, Wei X, Xie Y. Tai chi for treating osteopenia and primary osteoporosis: a meta-analysis and trial sequential analysis. Clin Interv Aging 2019; 14:91-104. [PMID: 30655662 PMCID: PMC6322510 DOI: 10.2147/cia.s187588] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Purpose The aim of this meta-analysis was to evaluate the efficacy of Tai chi (TC) as an adjuvant treatment for osteopenia and primary osteoporosis. Methods We went through eight databases to identify relevant randomized controlled trials that compared TC with a control group. The primary outcome was osteoporosis-related fractures (fracture incidence). Meta-analyses and trial sequential analyses (TSA) were conducted using RevMan 5.3 and TSA 0.9. Results Fifteen randomized controlled trials involving a total of 857 patients were included in the analyses. No trials reported primary outcome; however, bone mineral density (BMD) values differed significantly in subgroup 1 (TC vs no treatment; weighted mean difference [WMD] =0.05 g/cm2, 95% CI 0.03 to 0.07; P<0.00001; P for heterogeneity =0.22, I2=22%) and subgroup 2 (TC vs conventional treatments; WMD =0.16 g/cm2, 95% CI 0.11 to 0.21; P<0.00001; P for heterogeneity =0.008, I2=75%). In addition, two trials compared TC with conventional treatments, which found a significant difference in bone gla protein (standardized mean difference =−1.18, 95% CI −1.66 to −0.70; P<0.00001; P for heterogeneity =0.58, I2=75%). The results of the BMD were confirmed by TSA. Also, TC may have a certain effect on the relief of osteoporotic pain (WMD = −2.61, 95% CI −3.51 to −1.71; WMD = −1.39, 95% CI −2.01 to −0.77). However, it did not promote the quality of life, level of serum calcium, serum phosphorus, and also had no effect on bone turnover markers. Conclusion Although there is no study monitoring fracture incidence, TC may be beneficial for patients in improving BMD values, level of bone gla protein, and relieving osteoporotic pain. However, due to the low methodological quality, current evidence for treating osteopenia and primary osteoporosis through TC is insufficient.
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Affiliation(s)
- Yili Zhang
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China, .,School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yan Chai
- Department of Epidemiology, University of California, Los Angeles, CA, USA
| | - Xiaojie Pan
- Department of Human Nutrition and Health, Wageningen University and Health, Wageningen, The Netherlands
| | - Hao Shen
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China,
| | - Xu Wei
- Department of Scientific Research, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China,
| | - Yanming Xie
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China,
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Falck RS, Best JR, Li LC, Chan PCY, Feehan LM, Liu-Ambrose T. Can we improve cognitive function among adults with osteoarthritis by increasing moderate-to-vigorous physical activity and reducing sedentary behaviour? Secondary analysis of the MONITOR-OA study. BMC Musculoskelet Disord 2018; 19:447. [PMID: 30577819 PMCID: PMC6303889 DOI: 10.1186/s12891-018-2369-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Accepted: 12/03/2018] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Preliminary evidence suggests osteoarthritis is a risk factor for cognitive decline. One potential reason is 87% of adults with osteoarthritis are inactive, and low moderate-to-vigorous physical activity and high sedentary behaviour are each risk factors for cognitive decline. Thus, we investigated whether a community-based intervention to increase moderate-to-vigorous physical activity and reduce sedentary behaviour could improve cognitive function among adults with osteoarthritis. METHODS This was a secondary analysis of a six month, proof-of-concept randomized controlled trial of a community-based, technology-enabled counselling program to increase moderate-to-vigorous physical activity and reduce sedentary behaviour among adults with knee osteoarthritis. The Immediate Intervention (n = 30) received a Fitbit® Flex™ and four bi-weekly activity counselling sessions; the Delayed Intervention (n = 31) received the same intervention two months later. We assessed episodic memory and working memory using the National Institutes of Health Toolbox Cognition Battery. Between-group differences (Immediate Intervention vs. Delayed Intervention) in cognitive performance were evaluated following the primary intervention (i.e., Baseline - 2 Months) using intention-to-treat. RESULTS The intervention did not significantly improve cognitive function; however, we estimated small average improvements in episodic memory for the Immediate Intervention vs. Delayed Intervention (estimated mean difference: 1.27; 95% CI [- 9.27, 11.81]; d = 0.10). CONCLUSION This small study did not show that a short activity promotion intervention improved cognitive health among adults with osteoarthritis. However, the effects of increased moderate-to-vigorous physical activity and reduced sedentary behaviour are likely to be small and thus we recommend subsequent studies use larger sample sizes and measure changes in cognitive function over longer intervals. TRIAL REGISTRATION NUMBER ClinicalTrials.gov Protocol Registration System: NCT02315664 ; registered 12 December, 2014; https://clinicaltrials.gov/ct2/show/NCT02315664?cond=NCT02315664&rank=1.
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Affiliation(s)
- Ryan S. Falck
- Faculty of Medicine, Aging, Mobility and Cognitive Neuroscience Laboratory, Djavad Mowafaghian Centre for Brain Health, Department of Physical Therapy, University of British Columbia, 212-2177 Wesbrook Mall, Vancouver, BC V6T 1Z3 Canada
| | - John R. Best
- Faculty of Medicine, Aging, Mobility and Cognitive Neuroscience Laboratory, Djavad Mowafaghian Centre for Brain Health, Department of Physical Therapy, University of British Columbia, 212-2177 Wesbrook Mall, Vancouver, BC V6T 1Z3 Canada
| | - Linda C. Li
- Faculty of Medicine, Arthritis Research Canada, University of British Columbia, Vancouver, Canada
| | - Patrick C. Y. Chan
- Faculty of Medicine, Aging, Mobility and Cognitive Neuroscience Laboratory, Djavad Mowafaghian Centre for Brain Health, Department of Physical Therapy, University of British Columbia, 212-2177 Wesbrook Mall, Vancouver, BC V6T 1Z3 Canada
| | - Lynne M. Feehan
- Faculty of Medicine, Arthritis Research Canada, University of British Columbia, Vancouver, Canada
| | - Teresa Liu-Ambrose
- Faculty of Medicine, Aging, Mobility and Cognitive Neuroscience Laboratory, Djavad Mowafaghian Centre for Brain Health, Department of Physical Therapy, University of British Columbia, 212-2177 Wesbrook Mall, Vancouver, BC V6T 1Z3 Canada
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Aytekin K, Erhan SŞ, Erişgin Z, Esenyel CZ, Takır S. Intra-articular injection of hydrogen sulfide decreased the progression of gonarthrosis. Can J Physiol Pharmacol 2018; 97:47-54. [PMID: 30521368 DOI: 10.1139/cjpp-2018-0574] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Hydrogen sulfide (H2S) is found in both the plasma and synovial fluid of patients with gonarthrosis. In the present study, we investigated whether intra-articular injection of sodium hydrosulfide (NaSH) (1 mM, 30 μL), a H2S donor, might affect gonarthrosis in rats. Gonarthrosis was induced surgically in the left knees of rats and left for 6 weeks for the development of disease. Then, intra-articular injections of NaSH or methylprednisolone (1 mg/kg, 30 μL) were administered to rats. Half of each group was sacrificed at the end of the first day and the other half was sacrificed at the end of 4 weeks to evaluate early and later effects of injections on gonarthrosis. The injury induced by anterior cruciate ligament resection and medial meniscectomy in rats caused the development of gonarthrosis. As the duration lengthened after gonarthrosis induction, the progression of the disease continued. According to the modified Mankin Scoring System, intra-articular injection of NaSH histopathologically slowed the progression of gonarthrosis, whereas methylprednisolone was ineffective. In addition, NaSH decreased apoptosis in rat knees with gonarthrosis. Each treatment did not cause injury to healthy knees. Our results lead to the consideration that intra-articular NaSH administration may be effective in the progression of gonarthrosis.
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Affiliation(s)
- Kürşad Aytekin
- a Department of Orthopedics and Traumatology, University of Giresun, Giresun, Turkey.,e Department of Anatomy, University of Giresun, Giresun, Turkey
| | - Selma Şengiz Erhan
- b Department of Pathology, Okmeydanı Research and Training Hospital, Istanbul, Turkey
| | - Züleyha Erişgin
- c Department of Histology and Embryology, University of Giresun, Giresun, Turkey
| | - Cem Zeki Esenyel
- a Department of Orthopedics and Traumatology, University of Giresun, Giresun, Turkey
| | - Selçuk Takır
- d Department of Pharmacology, University of Giresun, Giresun, Turkey
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Tang L, Ding J, Zhou G, Liu Z. LncRNA‑p21 promotes chondrocyte apoptosis in osteoarthritis by acting as a sponge for miR‑451. Mol Med Rep 2018; 18:5295-5301. [PMID: 30272288 DOI: 10.3892/mmr.2018.9506] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 09/11/2018] [Indexed: 11/05/2022] Open
Abstract
Osteoarthritis (OA) is the most common type of arthritis, and remains to be social and medical challenge. Thus, identifying novel molecular targets is important for the prevention and treatment of OA. Long noncoding RNAs (lncRNAs) have been reported to modulate various biological and pathological processes. The aim of the present study was to investigate the role of lncRNA‑p21 in OA and its underlying mechanism, in order to better understand the development of OA and its treatment. Chondrocytes were isolated from cartilage samples obtained from OA and normal patients. Chondrocytes were transfected with microRNA (miRNA/miR)‑451 mimics, miR‑451 inhibitor, pcDNA3.1(+)‑p21 or small interfering RNA‑p21. Flow cytometry was performed to analyze cell apoptosis and reverse transcription‑quantitative polymerase chain reaction was conducted to detect the expression of mRNAs and miRNAs. Cell Counting Kit‑8 assay was performed to detect cell viability. The results revealed that the level of lncRNA‑p21 was significantly upregulated in OA cartilage when compared with the normal cartilage. Silencing of lncRNA‑p21 increased cell viability and inhibited the apoptosis rate of chondrocytes in OA, while lncRNA‑p21 overexpression decreased cell viability and increased the apoptosis rate of chondrocytes in OA. Overexpression of lncRNA‑p21 suppressed the expression of miR‑451 while the silencing of lncRNA‑p21 reversed this effect. MiR‑451 inhibitor effectively inhibited the upregulatory effect of si‑p21 on miR‑451. The increased cell viability and decreased apoptosis rate induced by lncRNA‑p21 silencing was abolished by the miR‑451 inhibitor. MiR‑451 mimic effectively increased the downregulatory effect of pcDNA3.1‑lncRNA‑p21 on miR‑451. The decreased cell viability and increased apoptosis rate induced by the overexpression of lncRNA‑p21 was abolished by the miR‑451 mimic. Investigation into the underlying mechanism revealed that lncRNA‑p21 interacted with miRNA‑451. In addition, lncRNA‑p21 negatively regulated the expression of miR‑451. Furthermore, lncRNA‑p21 promoted the apoptosis of chondrocytes in OA by acting as a sponge for miR‑451. Thus, lncRNA‑p21 was proposed as a promising target for the treatment of OA.
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Affiliation(s)
- Luping Tang
- Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
| | - Jianbo Ding
- Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
| | - Guangju Zhou
- Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
| | - Zhihai Liu
- Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
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Reddi S, Mada SB, Kumar N, Kumar R, Ahmad N, Karvande A, Kapila S, Kapila R, Trivedi R. Antiosteopenic Effect of Buffalo Milk Casein-Derived Peptide (NAVPITPTL) in Ovariectomized Rats. Int J Pept Res Ther 2018. [DOI: 10.1007/s10989-018-9763-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Ning D, Jin M, Xv T, Sun J, Li M. Homoisoflavanone-1 isolated from Polygonatum odoratum arrests the cell cycle and induces apoptosis in A549 cells. Oncol Lett 2018; 16:3545-3554. [PMID: 30127960 PMCID: PMC6096101 DOI: 10.3892/ol.2018.9085] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 06/28/2018] [Indexed: 02/06/2023] Open
Abstract
Homoisoflavanone-1 is a natural compound that may be extracted from the Chinese medicinal herb Polygonatum odoratum, which has pronounced antioxidant activities. The present study reports that homoisoflavanone-1 significantly inhibited tumor cell growth and induced apoptosis in A549 non-small cell lung cancer (NSCLC) cells in a dose-dependent manner. Homoisoflavanone-1 arrested the cell cycle at the G2/M stage, which was associated with an increase in the accumulation of phosphorylated (p-)p38, p38, p53, and p-cyclin dependent kinase (Cdc)2 proteins, as well as a decrease in Cdc2 expression. In addition, treatment with homoisoflavanone-1 increased the levels of active caspase-3 and decreased Poly ADP-ribose polymerase, which was accompanied by a reduction in the B-cell lymphoma-2/Bak ratio and consequently, apoptosis. Furthermore, homoisoflavanone-1 increased the expression of endoplasmic reticulum (ER) stress-related proteins, including PERK, ATF4 and GADD34 in a dose-dependent manner. In conclusion, homoisoflavanone-1 induced apoptosis in A549 cells by regulating the mitochondria-caspase-dependent and ER stress pathways and resulted in G2/M arrest by activating the p38/p53 signaling pathway. These findings suggest that homoisoflavanone-1 extracted from Polygonatum odoratum may function as a cancer-suppressing agent and has potential as a novel therapeutic method against NSCLC.
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Affiliation(s)
- Deli Ning
- Department of Pharmacy, The Institute of Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China
| | - Ming Jin
- Department of Pharmacy, The Institute of Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China
| | - Tao Xv
- Department of Pharmacy, The Institute of Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China
| | - Jikai Sun
- Department of Pharmacy, The Institute of Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China
| | - Min Li
- Department of Pharmacy, The Institute of Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China
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Huang Y, Cai GQ, Peng JP, Shen C. Glucocorticoids induce apoptosis and matrix metalloproteinase-13 expression in chondrocytes through the NOX4/ROS/p38 MAPK pathway. J Steroid Biochem Mol Biol 2018. [PMID: 29526705 DOI: 10.1016/j.jsbmb.2018.03.001] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Based on the results from our previous study, dexamethasone (Dex) increases reactive oxygen species (ROS) levels and subsequently induces cell death and matrix catabolism in chondrocytes. Nevertheless, the mechanism underlying this phenomenon remains unclear. Nicotinamide adenine dinucleotide (phosphate) (NADPH) oxidase 4 (NOX4) is one of the major enzymes responsible for intracellular ROS production during the inflammatory process. The objective of the current study was to investigate the role of NOX4 in Dex-induced ROS over-production. Healthy chondrocytes were harvested from the cartilage debris from 6 female patients. NOX4 and p38 mitogen-activated protein kinase (MAPK) expression levels in these cells were evaluated in the presence of Dex. Changes in the number of apoptotic and viable Dex-treated chondrocytes were recorded after the cells were treated with NOX and p38 MAPK inhibitors. Changes in matrix metalloproteinase 13 (MMP-13) expression levels in Dex-treated chondrocytes were also investigated. The Dex treatment increased NOX4 expression via the glucocorticoid receptor (GR). Treatment of cells with apocynin, a NOX inhibitor, decreased intracellular ROS levels and inhibited p38 MAPK activation. Treatment of cells with a ROS scavenger also reduced p38 MAPK expression. Treatment of cells with a NOX inhibitor, ROS scavenger and p38 MAPK inhibitor rescued chondrocytes from Dex-induced apoptosis. Moreover, treatment of cells with these agents blocked MMP-13 expression in Dex-treated chondrocytes. NOX4 silencing also suppressed p38 MAPK and MMP-13 expression. Dex triggered apoptosis and MMP-13 expression through the NOX4/ROS/p38 MAPK signaling pathway. NOX4 may be a therapeutic target in the management of Dex-induced complications.
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Affiliation(s)
- Ying Huang
- Department of Anesthesiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China
| | - Gui-Quan Cai
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China
| | - Jian-Ping Peng
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China
| | - Chao Shen
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China.
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Yang Z, Tang Y, Lu H, Shi B, Ye Y, Xu G, Zhao Q. Long non-coding RNA reprogramming (lncRNA-ROR) regulates cell apoptosis and autophagy in chondrocytes. J Cell Biochem 2018; 119:8432-8440. [PMID: 29893429 DOI: 10.1002/jcb.27057] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 04/23/2018] [Indexed: 12/14/2022]
Abstract
Long Non-Coding RNA Reprogramming (lncRNA-ROR) plays an important role in regulating various biologic processes, whereas the effect of lncRNA-ROR in osteoarthritis (OA) is little studied. This study aimed to explore lncRNA-ROR expression in articular cartilage and identify the functional mechanism of lncRNA-ROR in OA. OA cartilage tissues were obtained from 15 OA patients, and 6 normal cartilage tissues were set as controls. Chondrocytes were isolated from the collected cartilage tissues. lncRNA-ROR was knockdown in normal cells and overexpressed in OA cells. Cell viability was determined with Cell Counting Kit-8 assay, and apoptosis was measured using flow cytometric analysis. Moreover, proteins and mRNAs involved in this study were also measured using Western blotting and quantitative real-time PCR (qPCR). Level of lncRNA-ROR was decreased in OA compared with normal chondrocytes, and overexpression of lncRNA-ROR dramatically promoted cell viability of OA chondrocytes. In addition, knockdown lncRNA-ROR inhibited apoptosis and promoted autophagy of normal chondrocytes. Moreover, lncRNA-ROR inhibited the expression of p53 in both mRNA and protein levels. Furthermore, we revealed that lncRNA-ROR regulated apoptosis and autophagy of chondrocytes via HIF1α and p53. The results indicated that lncRNA-ROR played a critical role in the pathogenesis of OA, suggesting that lncRNA-ROR could serve as a new potential therapeutic target for OA.
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Affiliation(s)
- Zhongmeng Yang
- Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Yuxing Tang
- Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Huading Lu
- Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Bo Shi
- Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Yongheng Ye
- Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Guoyong Xu
- Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Qing Zhao
- Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
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Sun J, Wei X, Wang Z, Liu Y, Lu J, Lu Y, Cui M, Zhang X, Li F. Inflammatory milieu cultivated Sema3A signaling promotes chondrocyte apoptosis in knee osteoarthritis. J Cell Biochem 2017; 119:2891-2899. [DOI: 10.1002/jcb.26470] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2017] [Accepted: 10/26/2017] [Indexed: 12/25/2022]
Affiliation(s)
- Jie Sun
- Department of Orthopaedic TraumaTianjin HospitalTianjinChina
| | - Xuelei Wei
- Department of Orthopaedic TraumaTianjin HospitalTianjinChina
| | - Zengliang Wang
- Department of Orthopaedic TraumaTianjin HospitalTianjinChina
| | - Yunjiao Liu
- Department of Orthopaedic TraumaTianjin HospitalTianjinChina
| | - Jie Lu
- Department of Orthopaedic TraumaTianjin HospitalTianjinChina
| | - Yandong Lu
- Department of Orthopaedic TraumaTianjin HospitalTianjinChina
| | - Meng Cui
- Department of Orthopaedic TraumaTianjin HospitalTianjinChina
| | - Xi Zhang
- Department of Orthopaedic TraumaTianjin HospitalTianjinChina
| | - Fangguo Li
- Department of Orthopaedic TraumaTianjin HospitalTianjinChina
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Janune D, Abd El Kader T, Aoyama E, Nishida T, Tabata Y, Kubota S, Takigawa M. Novel role of CCN3 that maintains the differentiated phenotype of articular cartilage. J Bone Miner Metab 2017; 35:582-597. [PMID: 27853940 DOI: 10.1007/s00774-016-0793-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Accepted: 09/25/2016] [Indexed: 02/07/2023]
Abstract
Knowledge of the microenvironment of articular cartilage in health and disease is the key to accomplishing fundamental disease-modifying treatments for osteoarthritis. The proteins comprising the CCN Family are matricellular proteins with a remarkable relevance within the context of cartilage metabolism. CCN2 displays a great capability for regenerating articular cartilage, and CCN3 has been shown to activate the expression of genes related to articular chondrocytes and to repress genes related to endochondral ossification in epiphyseal chondrocytes. Moreover, mice lacking CCN3 protein have been shown to display ostearthritic changes in their knee articular cartilage. In this study, we employed a monoiodoacetic acid (MIA)-induced osteoarthritic model to investigate whether osteoarthritic changes in the cartilage are reciprocally accompanied by CCN3 down-regulation and an inducible overexpression system to evaluate the effects of CCN3 on articular chondrocytes in vitro. Finally, we also investigated the effects of exogenous CCN3 in vivo during the early stages of MIA-induced osteoarthritis. We discovered that CCN3 is expressed by articular chondrocytes in normal rat knees, whereas it is rapidly down-regulated in osteoarthritic knees. In vitro, we also discovered that CCN3 increases the proteoglycan accumulation, the gene expression of type II collagen, tenascin-C and lubricin, as well as the protein production of tenascin-C and lubricin in articular chondrocytes. In vivo, it was discovered that exogenous CCN3 increased tidemark integrity and produced an increased production of lubricin protein. The potential utility of CCN3 as a future therapeutic agent and possible strategies to improve its therapeutic functions are also discussed.
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Affiliation(s)
- Danilo Janune
- Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, Okayama, Japan
- Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan
| | - Tarek Abd El Kader
- Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, Okayama, Japan
| | - Eriko Aoyama
- Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, Okayama, Japan
| | - Takashi Nishida
- Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan
| | - Yasuhiko Tabata
- Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
| | - Satoshi Kubota
- Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, Okayama, Japan.
- Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.
| | - Masaharu Takigawa
- Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, Okayama, Japan.
- Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.
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Chen Y, Huang J, Tang C, Chen X, Yin Z, Heng BC, Chen W, Shen W. Small molecule therapeutics for inflammation-associated chronic musculoskeletal degenerative diseases: Past, present and future. Exp Cell Res 2017; 359:1-9. [PMID: 28739444 DOI: 10.1016/j.yexcr.2017.07.027] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 07/19/2017] [Accepted: 07/21/2017] [Indexed: 12/13/2022]
Abstract
Inflammation-associated chronic musculoskeletal degenerative diseases (ICMDDs) like osteoarthritis and tendinopathy often results in morbidity and disability, with consequent heavy socio-economic burden. Current available therapies such as NSAIDs and glucocorticoid are palliative rather than disease-modifying. Insufficient systematic research data on disease molecular mechanism also makes it difficult to exploit valid therapeutic targets. Small molecules are designed to act on specific signaling pathways and/or mechanisms of cellular physiology and function, and have gradually shown potential for treating ICMDDs. In this review, we would examine and analyze recent developments in small molecule drugs for ICMDDs, suggest possible feasible improvements in treatment modalities, and discuss future research directions.
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Affiliation(s)
- Yangwu Chen
- Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310009, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Orthopaedics Research Institute of Zhejiang Univerisity, China; Department of Sports Medicine, School of Medicine, Zhejiang University, Zhejiang 310000, China; China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China
| | - Jiayun Huang
- Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310009, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Orthopaedics Research Institute of Zhejiang Univerisity, China; Department of Sports Medicine, School of Medicine, Zhejiang University, Zhejiang 310000, China; China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China
| | - Chenqi Tang
- Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310009, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Orthopaedics Research Institute of Zhejiang Univerisity, China; Department of Sports Medicine, School of Medicine, Zhejiang University, Zhejiang 310000, China; China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China
| | - Xiao Chen
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Department of Sports Medicine, School of Medicine, Zhejiang University, Zhejiang 310000, China; China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China
| | - Zi Yin
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Department of Sports Medicine, School of Medicine, Zhejiang University, Zhejiang 310000, China
| | - Boon Chin Heng
- Faculty of Dentistry, Department of Endodontology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Weishan Chen
- Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310009, China; Orthopaedics Research Institute of Zhejiang Univerisity, China.
| | - Weiliang Shen
- Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310009, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang 310000, China; Orthopaedics Research Institute of Zhejiang Univerisity, China; Department of Sports Medicine, School of Medicine, Zhejiang University, Zhejiang 310000, China; China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China.
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Mierzwa AGH, Campos JF, Jesus MF, Nader HB, Lazaretti-Castro M, Reginato RD. Different doses of strontium ranelate and mechanical vibration modulate distinct responses in the articular cartilage of ovariectomized rats. Osteoarthritis Cartilage 2017; 25:1179-1188. [PMID: 28223125 DOI: 10.1016/j.joca.2017.02.793] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Revised: 02/07/2017] [Accepted: 02/09/2017] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To investigate the effects of different strontium ranelate (SrR) doses alone or in combination with low-intensity and high-frequency mechanical vibration (MV) on articular cartilage in ovariectomized rats. DESIGN Fifty 6-month-old female Wistar rats underwent ovariectomy (OVX) and after 3 months were divided into: control group (Control); SrR 300 mg/kg/day (SrR300); SrR 625 mg/kg/day (SrR625); MV; SrR 625 mg/kg/day plus MV (SrR625 + MV). The vehicle and the SrR were administered by gavage 7 days/week and vibration (0.6 g/60 Hz) was performed for 20 min/day, 5 days/week. Bone mineral density (BMD) and body composition were evaluated by densitometry. Changes in cartilage were assessed 90 days after treatment by histomorphometry; immunohistochemistry analysis evaluating cell death (caspase-3), tumor necrosis factor-α (TNF-α), metalloproteinase 9 (MMP-9) and type II collagen; Osteoarthritis Research Society International (OARSI) grading system and glycosaminoglycans (GAGs) analyses. RESULTS SrR-treated groups exhibited a lower OARSI grade, a smaller number of chondrocyte clusters, increased levels of chondroitin sulfate (CS) and decreased expression of caspase-3. Additionally, compared to all the groups, SrR300 exhibited increased levels of hyaluronic acid (HA). Vibration applied alone or in combination accelerated cartilage degradation, as demonstrated by increased OARSI grade, reduced number of chondrocytes, increased number of clusters, elevated expression of type II collagen and cell death, and was accompanied by decreased amounts of CS and HA; however, MV alone was able to reduce MMP-9. CONCLUSIONS SrR and vibration modulate distinct responses in cartilage. Combined treatment accelerates degeneration. In contrast, SrR treatment at 300 mg/kg/day attenuates osteoarthritis (OA) progression, improving cartilage matrix quality and preserving cell viability in ovariectomized rats.
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Affiliation(s)
- A G H Mierzwa
- Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
| | - J F Campos
- Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
| | - M F Jesus
- Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
| | - H B Nader
- Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
| | - M Lazaretti-Castro
- Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
| | - R D Reginato
- Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
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Yang J, Wu Q, Lv J, Nie H. 4-Phenyl butyric acid prevents glucocorticoid-induced osteoblast apoptosis by attenuating endoplasmic reticulum stress. J Bone Miner Metab 2017; 35:366-374. [PMID: 27678165 DOI: 10.1007/s00774-016-0778-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2016] [Accepted: 08/08/2016] [Indexed: 12/15/2022]
Abstract
Apoptosis of osteoblasts triggered by high-dose glucocorticoids (GCs) has been identified as a major cause of osteoporosis. However, the molecular mechanisms underlying GC-induced osteoporosis remain elusive. This study was conducted to make clear the mechanism of GC-induced osteoblast apoptosis and to examine whether reduction of ER stress by 4-PBA inhibited osteoblast apoptosis. After treatment with dexamethasone (Dex) or hydrocortisone, cell viability was assessed using an MTT assay. Flow cytometry was performed to assess the apoptosis of MC3T3-E1 cells. The expression levels of ER stress-related proteins (CHOP, GRP78, eIF2α, and phospho-eIF2α) and apoptosis-related proteins (cleaved Caspase-3, Bcl-2, and Bax) in MC3T3-E1 cells were measured by Western blot analysis. We found that both Dex and hydrocortisone reduced cell proliferation and promoted apoptosis in MC3T3-E1 cells. In addition, the protein expression levels of cleaved Caspase-3 and Bax increased and the protein expression level of Bcl-2 decreased in MC3T3-E1 cells exposed to Dex. In addition, the Dex exposure also resulted in a release of cytochrome c (Cyt C) from mitochondria. The cellular ATP content was decreased following prolonged treatment with Dex. 4-PBA attenuated ER stress and mitochondrial dysfunction induced by Dex in MC3T3-E1 cells. Dex-mediated apoptosis of MC3T3-E1 cells is aggravated by ER stress. Moreover, Dex-induced apoptosis in MC3T3-E1 cells was inhibited by 4-PBA, suggesting that ER stress involved in Dex-induced apoptosis. In conclusion, inhibition of ER stress by 4-PBA could reduce GC-induced apoptosis in MC3T3-E1 cells.
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Affiliation(s)
- Jianhui Yang
- Rehabilitation Center, The First Affiliated Hospital of Health Science Center, Xi'an Jiaotong University, No 277 Yanta West Road, Xi'an, 710061, Shaanxi Province, China.
| | - Qiong Wu
- Rehabilitation Center, The First Affiliated Hospital of Health Science Center, Xi'an Jiaotong University, No 277 Yanta West Road, Xi'an, 710061, Shaanxi Province, China
| | - Jianguo Lv
- Rehabilitation Center, The First Affiliated Hospital of Health Science Center, Xi'an Jiaotong University, No 277 Yanta West Road, Xi'an, 710061, Shaanxi Province, China
| | - Huiyong Nie
- Rehabilitation Center, The First Affiliated Hospital of Health Science Center, Xi'an Jiaotong University, No 277 Yanta West Road, Xi'an, 710061, Shaanxi Province, China
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Szychlinska MA, Castrogiovanni P, Nsir H, Di Rosa M, Guglielmino C, Parenti R, Calabrese G, Pricoco E, Salvatorelli L, Magro G, Imbesi R, Mobasheri A, Musumeci G. Engineered cartilage regeneration from adipose tissue derived-mesenchymal stem cells: A morphomolecular study on osteoblast, chondrocyte and apoptosis evaluation. Exp Cell Res 2017; 357:222-235. [PMID: 28529106 DOI: 10.1016/j.yexcr.2017.05.018] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Revised: 04/23/2017] [Accepted: 05/18/2017] [Indexed: 02/08/2023]
Abstract
The poor self-repair capacity of cartilage tissue in degenerative conditions, such as osteoarthritis (OA), has prompted the development of a variety of therapeutic approaches, such as cellular therapies and tissue engineering based on the use of mesenchymal stem cells (MSCs). The aim of this study is to demonstrate, for the first time, that the chondrocytes differentiated from rat adipose tissue derived-MSCs (AMSCs), are able to constitute a morphologically and biochemically healthy hyaline cartilage after 6 weeks of culture on a Collagen Cell Carrier (CCC) scaffold. In this study we evaluated the expression of some osteoblasts (Runt-related transcription factor 2 (RUNX2) and osteocalcin), chondrocytes (collagen I, II and lubricin) and apoptosis (caspase-3) biomarkers in undifferentiated AMSCs, differentiated AMSCs in chondrocytes cultured in monolayer and AMSCs-derived chondrocytes seeded on CCC scaffolds, by different techniques such as immunohistochemistry, ELISA, Western blot and gene expression analyses. Our results showed the increased expression of collagen II and lubricin in AMSCs-derived chondrocytes cultured on CCC scaffolds, whereas the expression of collagen I, RUNX2, osteocalcin and caspase-3 resulted decreased, when compared to the controls. In conclusion, this innovative basic study could be a possible key for future therapeutic strategies for articular cartilage restoration through the use of CCC scaffolds, to reduce the morbidity from acute cartilage injuries and degenerative joint diseases.
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Affiliation(s)
- Marta Anna Szychlinska
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy
| | - Paola Castrogiovanni
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy
| | - Houda Nsir
- Biotechnology Laboratory of Olive Tree, Centre of Biotechnology of Borj Cedreya, University of Carthage, Tunisia
| | - Michelino Di Rosa
- Department of Biomedical and Biotechnological Sciences, Pathology Section, School of Medicine, University of Catania, Catania, Italy
| | - Claudia Guglielmino
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy
| | - Rosalba Parenti
- Department of Biomedical and Biotechnological Sciences, Physiology Section, School of Medicine, University of Catania, Catania, Italy
| | - Giovanna Calabrese
- Department of Biomedical and Biotechnological Sciences, Physiology Section, School of Medicine, University of Catania, Catania, Italy
| | - Elisabetta Pricoco
- Department of Medical and Surgical Sciences and Advanced Technologies, Anatomic Pathology Section, School of Medicine, University of Catania, Catania, Italy
| | - Lucia Salvatorelli
- Department of Medical and Surgical Sciences and Advanced Technologies, Anatomic Pathology Section, School of Medicine, University of Catania, Catania, Italy
| | - Gaetano Magro
- Department of Medical and Surgical Sciences and Advanced Technologies, Anatomic Pathology Section, School of Medicine, University of Catania, Catania, Italy
| | - Rosa Imbesi
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy
| | - Ali Mobasheri
- The D-BOARD European Consortium for Biomarker Discovery, The APPROACH Innovative Medicines Initiative (IMI) Consortium, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Duke of Kent Building, Guildford GU2 7XH, Surrey, United Kingdom; Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), King AbdulAziz University, Jeddah 21589, Saudi Arabia; Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Arthritis Research UK Pain Centre, Medical Research Council and Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom
| | - Giuseppe Musumeci
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy; Department of Health, Institut des Etudes Universitaries, UniPoliSI, Veyras, Switzerland.
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Jørgensen AEM, Kjær M, Heinemeier KM. The Effect of Aging and Mechanical Loading on the Metabolism of Articular Cartilage. J Rheumatol 2017; 44:410-417. [PMID: 28250141 DOI: 10.3899/jrheum.160226] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/11/2017] [Indexed: 12/25/2022]
Abstract
OBJECTIVE The morphology of articular cartilage (AC) enables painless movement. Aging and mechanical loading are believed to influence development of osteoarthritis (OA), yet the connection remains unclear. METHODS This narrative review describes the current knowledge regarding this area, with the literature search made on PubMed using appropriate keywords regarding AC, age, and mechanical loading. RESULTS Following skeletal maturation, chondrocyte numbers decline while increasing senescence occurs. Lower cartilage turnover causes diminished maintenance capacity, which produces accumulation of fibrillar crosslinks by advanced glycation end products, resulting in increased stiffness and thereby destruction susceptibility. CONCLUSION Mechanical loading changes proteoglycan content. Moderate mechanical loading causes hypertrophy and reduced mechanical loading causes atrophy. Overloading produces collagen network damage and proteoglycan loss, leading to irreversible cartilage destruction because of lack of regenerative capacity. Catabolic pathways involve inflammation and the transcription factor nuclear factor-κB. Thus, age seems to be a predisposing factor for OA, with mechanical overload being the likely triggering cause.
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Affiliation(s)
- Adam El Mongy Jørgensen
- From the Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, and the Department of Biomedical Sciences, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. .,A.E. Jørgensen, MD, Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen; M. Kjær, MD, DMSc, Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen; K.M. Heinemeier, MSc, PhD, Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, and Department of Biomedical Sciences, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen.
| | - Michael Kjær
- From the Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, and the Department of Biomedical Sciences, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,A.E. Jørgensen, MD, Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen; M. Kjær, MD, DMSc, Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen; K.M. Heinemeier, MSc, PhD, Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, and Department of Biomedical Sciences, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen
| | - Katja Maria Heinemeier
- From the Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, and the Department of Biomedical Sciences, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,A.E. Jørgensen, MD, Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen; M. Kjær, MD, DMSc, Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen; K.M. Heinemeier, MSc, PhD, Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital, and Department of Biomedical Sciences, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen
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Effect of buffalo casein-derived novel bioactive peptides on osteoblast differentiation. Eur J Nutr 2016; 57:593-605. [DOI: 10.1007/s00394-016-1346-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 11/10/2016] [Indexed: 12/17/2022]
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Leonardi R, Perrotta RE, Almeida LE, Loreto C, Musumeci G. Lubricin in synovial fluid of mild and severe temporomandibular joint internal derangements. Med Oral Patol Oral Cir Bucal 2016; 21:e793-e799. [PMID: 27694778 PMCID: PMC5116123 DOI: 10.4317/medoral.21145] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 04/11/2016] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND To understand the molecular basis of temporomandibular joint (TMJ) pathologies, we aimed to investigate the lubricin levels in the TMJ synovial fluid (SF) of patients with mild to severe internal derangements (IDs). MATERIAL AND METHODS A total, 34 joints were the study group. Only patients, with a Wilkes stage of III, IV and V were included, in this sample. Control group consisted of SF from eight joints, from patients undergoing to orthognatic surgery. Concentrations of lubricin in the SF from both samples were measured using ELISA system. RESULTS The mean lubricin concentration was 7.029 ± 0.21 µg/mL in stage III patients; 5.64 ± 0.10 µg/mL in stage IV patients, and 4.78 ± 0.11 µg/mL in stage V patients. The lubricin levels from stage IV and stage V patients differed significantly (P ≤ 0.001) from those of control subjects. Lubricin levels were inversely correlated with age and to VAS score. CONCLUSIONS The results of this cross-sectional study highlight the relationship between disease severity and the levels of lubricin in TMJ SF. Our findings suggest that novel biotherapeutic approaches, including the administration of recombinant lubricin in the joint cavity, for the treatment of TMJ diseases can be developed.
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Affiliation(s)
- R Leonardi
- University of Catania, Via S. Sofia 87, 95131, Catania, Italy,
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The Effects of Exercise and Kinesio Tape on Physical Limitations in Patients with Knee Osteoarthritis. J Funct Morphol Kinesiol 2016. [DOI: 10.3390/jfmk1040355] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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Bissinger O, Kreutzer K, Götz C, Hapfelmeier A, Pautke C, Vogt S, Wexel G, Wolff KD, Tischer T, Prodinger PM. A biomechanical, micro-computertomographic and histological analysis of the influence of diclofenac and prednisolone on fracture healing in vivo. BMC Musculoskelet Disord 2016; 17:383. [PMID: 27596101 PMCID: PMC5011804 DOI: 10.1186/s12891-016-1241-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Accepted: 09/01/2016] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) have long been suspected of negatively affecting fracture healing, although numerous disputes still exist and little data are available regarding diclofenac. Glucocorticoids interfere in this process over a similar and even broader mechanism of action. As many previously conducted studies evaluated either morphological changes or biomechanical properties of treated bones, the conjunction of both structural measures is completely missing. Therefore, it was our aim to evaluate the effects of diclofenac and prednisolone on the fracture callus biomechanically, morphologically and by 3-dimensional (3D) microstructural analysis. METHODS Femura of diclofenac-, prednisolone- or placebo-treated rats were pinned and a closed transverse fracture was generated. After 21 days, biomechanics, micro-CT (μCT) and histology were examined. RESULTS The diclofenac group showed significantly impaired fracture healing compared with the control group by biomechanics and μCT (e.g. stiffness: 57.31 ± 31.11 N/mm vs. 122.44 ± 81.16 N/mm, p = 0.030; callus volume: 47.05 ± 15.67 mm3 vs. 67.19 ± 14.90 mm3, p = 0.037, trabecular thickness: 0.0937 mm ± 0.003 vs. 0.0983 mm ± 0.003, p = 0.023), as confirmed by histology. Biomechanics of the prednisolone group showed obviously lower absolute values than the control group. These alterations were confirmed in conjunction with μCT and histology. CONCLUSIONS The inhibiting effects of both substances were not only mediated by absolute parameters (e.g. breaking load, BV), but we have shown, for the first time, that additional changes occurred in the microstructural bony network. Especially in patients at risk for delayed bone healing (arteriosclerosis, diabetes mellitus, smoking), the administration of these drugs should be weighed carefully.
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Affiliation(s)
- Oliver Bissinger
- Department of Oral and Maxillofacial Surgery, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
| | - Kilian Kreutzer
- Department of Oral and Maxillofacial Surgery, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Carolin Götz
- Department of Oral and Maxillofacial Surgery, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Alexander Hapfelmeier
- Institute of Medical Statistics and Epidemiology, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Christoph Pautke
- Department of Oral and Maxillofacial Surgery, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Stephan Vogt
- Department of Orthopaedics and Orthopaedic Sports Medicine, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany.,Department of Orthopaedic Sports Medicine, Hessing Stiftung Augsburg, Hessingstr. 17, 86199, Augsburg, Germany
| | - Gabriele Wexel
- Department of Orthopaedics and Orthopaedic Sports Medicine, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Klaus-Dietrich Wolff
- Department of Oral and Maxillofacial Surgery, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Thomas Tischer
- Department of Orthopaedics and Orthopaedic Sports Medicine, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany.,Department of Orthopaedic Surgery, University of Rostock, Doberanerstr. 142, 18057, Rostock, Germany
| | - Peter Michael Prodinger
- Department of Orthopaedics and Orthopaedic Sports Medicine, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
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Szychlinska MA, Leonardi R, Al-Qahtani M, Mobasheri A, Musumeci G. Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches. Ann Phys Rehabil Med 2016; 59:149-156. [PMID: 27118399 DOI: 10.1016/j.rehab.2016.03.005] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 02/16/2016] [Accepted: 03/09/2016] [Indexed: 01/15/2023]
Abstract
Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief.
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Affiliation(s)
- M A Szychlinska
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia 87, 95123 Catania, Italy
| | - R Leonardi
- Department of Medical and Surgical Science, Section of Dentistry, University of Catania, Catania, Italy
| | - M Al-Qahtani
- Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - A Mobasheri
- Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), King Abdulaziz University, Jeddah 21589, Saudi Arabia; The D-BOARD European Consortium for Biomarker Discovery, The APPROACH Innovative Medicines Initiative (IMI) Consortium, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Duke of Kent Building, Guildford GU2 7XH, Surrey, United Kingdom; Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Arthritis Research UK Pain Centre, Medical Research Council and Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom
| | - G Musumeci
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia 87, 95123 Catania, Italy.
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Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological, Immunohistochemical and Gene Expression Profiles. Int J Mol Sci 2016; 17:359. [PMID: 26978347 PMCID: PMC4813220 DOI: 10.3390/ijms17030359] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Revised: 02/16/2016] [Accepted: 02/22/2016] [Indexed: 12/17/2022] Open
Abstract
Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease.
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Nakagawa Y, Muneta T, Otabe K, Ozeki N, Mizuno M, Udo M, Saito R, Yanagisawa K, Ichinose S, Koga H, Tsuji K, Sekiya I. Cartilage Derived from Bone Marrow Mesenchymal Stem Cells Expresses Lubricin In Vitro and In Vivo. PLoS One 2016; 11:e0148777. [PMID: 26867127 PMCID: PMC4750963 DOI: 10.1371/journal.pone.0148777] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2015] [Accepted: 01/22/2016] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE Lubricin expression in the superficial cartilage will be a crucial factor in the success of cartilage regeneration. Mesenchymal stem cells (MSCs) are an attractive cell source and the use of aggregates of MSCs has some advantages in terms of chondrogenic potential and efficiency of cell adhesion. Lubricin expression in transplanted MSCs has not been fully elucidated so far. Our goals were to determine (1) whether cartilage pellets of human MSCs expressed lubricin in vitro chondrogenesis, (2) whether aggregates of human MSCs promoted lubricin expression, and (3) whether aggregates of MSCs expressed lubricin in the superficial cartilage after transplantation into osteochondral defects in rats. METHODS For in vitro analysis, human bone marrow (BM) MSCs were differentiated into cartilage by pellet culture, and also aggregated using the hanging drop technique. For an animal study, aggregates of BM MSCs derived from GFP transgenic rats were transplanted to the osteochondral defect in the trochlear groove of wild type rat knee joints. Lubricin expression was mainly evaluated in differentiated and regenerated cartilages. RESULTS In in vitro analysis, lubricin was detected in the superficial zone of the pellets and conditioned medium. mRNA expression of Proteoglycan4 (Prg4), which encodes lubricin, in pellets was significantly higher than that of undifferentiated MSCs. Aggregates showed different morphological features between the superficial and deep zone, and the Prg4 mRNA expression increased after aggregate formation. Lubricin was also found in the aggregate. In a rat study, articular cartilage regeneration was significantly better in the MSC group than in the control group as shown by macroscopical and histological analysis. The transmission electron microscope showed that morphology of the superficial cartilage in the MSC group was closer to that of the intact cartilage than in the control group. GFP positive cells remained in the repaired tissue and expressed lubricin in the superficial cartilage. CONCLUSION Cartilage derived from MSCs expressed lubricin protein both in vitro and in vivo. Aggregation promoted lubricin expression of MSCs in vitro and transplantation of aggregates of MSCs regenerated cartilage including the superficial zone in a rat osteochondral defect model. Our results indicate that aggregated MSCs could be clinically relevant for therapeutic approaches to articular cartilage regeneration with an appropriate superficial zone in the future.
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Affiliation(s)
- Yusuke Nakagawa
- Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Takeshi Muneta
- Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
| | - Koji Otabe
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Nobutake Ozeki
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mitsuru Mizuno
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mio Udo
- Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ryusuke Saito
- Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
| | - Katsuaki Yanagisawa
- Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shizuko Ichinose
- Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hideyuki Koga
- Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kunikazu Tsuji
- Department of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ichiro Sekiya
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan
- * E-mail:
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Musumeci G. Effects of exercise on physical limitations and fatigue in rheumatic diseases. World J Orthop 2015; 6:762-769. [PMID: 26601057 PMCID: PMC4644863 DOI: 10.5312/wjo.v6.i10.762] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Revised: 08/08/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
Physical activity covers not just sports but also simple everyday movements such as housework, walking and playing. Regular exercise has a great importance in maintaining good health, indeed inactivity is a risk factor for different chronic diseases. Physical exercise can play a crucial role in the treatment of rheumatic diseases, optimizing both physical and mental health, enhancing energy, decreasing fatigue and improving sleep. An exercise program for patients with rheumatic diseases aims to preserve or restore a range of motion of the affected joints, to increase muscle strength and endurance, and to improve mood and decrease health risks associated with a sedentary lifestyle. In this editorial I describe the benefits of the exercise on physical limitations and fatigue in rheumatic diseases that seem to have a short and long-term effectiveness. A literature review was conducted on PubMed, Scopus and Google Scholar using appropriate keywords based on the present editorial.
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