Pos0400 a causative role for periarticular skeletal muscle weakness in the progression of joint damage and pain in oa

Background Although OA is regarded as a disease of the articular cartilage, recent research has demonstrated whole-joint pathology, including synovial inflammation, subchondral bone sclerosis, osteophyte formation, and changes in periarticular muscles that surround the affected joint. There is also increasing evidence that the consequences of knee OA are associated with decreased lower limb muscle strength and function. It is unclear whether the change in periarticular muscle is the cause or result of disease progression, however. Objectives This study investigated changes in periarticular muscle during the progression of osteoarthritis (OA), as well as the cause-and-effect relationship between muscle weakness and OA, in a mouse model of OA achieved by destabilization of the medial meniscus (DMM). Methods Knee OA was induced by DMM in 10-week-old male C57BL/6 mice. Pathological muscle phenotypes in the tibialis anterior (TA) and quadriceps muscles were assessed in both the early and late stages of OA with muscle-fiber cross-sectional area analysis, markers of myogenesis, as well as the proliferation of satellite cells. OA pathology and pain behavior were examined with OARSI grade, von Frey filament threshold and pressure algometer. Periarticular muscle weakness was induced by multiple rounds of barium chloride injections after DMM induction. In addition, myostatin knockout.mice with muscle hypertrophy phenotype was used to evaluate the influence of muscle mass on pain and joint destruction after DMM. Results Morphological alterations in the TA and quadriceps in DMM mice included variations in muscle-fiber size, aberrant muscle fibrosis, inflammatory cell infiltration, and decreased muscle mass. Periarticular muscle fibers isolated from DMM mice showed reductions in cell number and myogenic capacity, as well as the proliferation of satellite cells. DMM mice exhibited exacerbated articular cartilage destruction, subchondral bone sclerosis, synovitis and pain after muscle injury compared to the DMM + vehicle group. Myostatin knockout mice were characterized by attenuated OA and the complete abrogation of pain behavior after DMM. Conclusion DMM-induced knee OA resulted in morphological changes in periarticular muscle, in a manner that coincided with muscle atrophy. Joint destruction and pain after DMM were aggravated by muscle weakness and alleviated by muscle hypertrophy. Our results suggest a causative role for muscle weakness in the progression of joint damage and pain in OA. References [1]Silva JMS, Alabarse PVG, Teixeira VON, et al. Muscle wasting in osteoarthritis model induced by anterior cruciate ligament transection. PLoS One 2018;13(4):e0196682. [2]Cunha JE, Barbosa GM, Castro P, et al. Knee osteoarthritis induces atrophy and neuromuscular junction remodeling in the quadriceps and tibialis anterior muscles of rats. Sci Rep 2019;9(1):6366. [3]Rehan Youssef A, Longino D, Seerattan R, et al. Muscle weakness causes joint degeneration in rabbits. Osteoarthritis Cartilage 2009;17(9):1228-35. [4]Noehren B, Kosmac K, Walton RG, et al. Alterations in quadriceps muscle cellular and molecular properties in adults with moderate knee osteoarthritis. Osteoarthritis Cartilage 2018;26(10):1359-68. [5]Baek KW, Jung YK, Kim JS, et al. Rodent Model of Muscular Atrophy for Sarcopenia Study. J Bone Metab 2020;27(2):97-110. [6]St Andre M, Johnson M, Bansal PN, et al. A mouse anti-myostatin antibody increases muscle mass and improves muscle strength and contractility in the mdx mouse model of Duchenne muscular dystrophy and its humanized equivalent, domagrozumab (PF-06252616), increases muscle volume in cynomolgus monkeys. Skelet Muscle 2017;7(1):2 Acknowledgements: NIL. Disclosure of Interests Hyun Ah Kim Consultant of: ICM Co., Ltd. Building 102, Room 455, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, ROK 2019- present Concultation on clinical aspect of RA and OA paid amount 5,000 per year, Hyun Sook Hwang: None declared, Ju-Ryoung Kim: None declared.