A causative role for periarticular skeletal muscle weakness in the progression of joint damage and pain in OA

Abstract

Abstract Although OA is regarded as a disease of the articular cartilage, recent research has demonstrated alterations in periarticular muscles that surround the affected joint. Here, we 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 by destabilization of the medial meniscus (DMM). Pathological phenotypes in the periarticular muscles were assessed in the early and late stages of OA by DMM. OA pathology and pain behavior in the mice after DMM induction were examined in response to periarticular muscle weakness induced by multiple rounds of barium chloride injections. The examinations were also performed in myostatin knockout mice with strengthened muscle phenotypes by muscle hypertrophy. Morphological alterations in the TA and quadriceps in DMM mice included variations in muscle-fiber size, aberrant ECM deposition, inflammatory cell infiltration, and decreased muscle mass. Periarticular muscle fibers isolated from DMM mice showed reductions in myoblast cell number and myogenic capacity, as well as the proliferation of satellite cells. DMM + muscle injury mice also showed exacerbated joint degeneration compared to the DMM vehicles. Myostatin knockout mice were characterized by attenuated OA and the complete abrogation of pain behavior after DMM. Our results suggest a causative role for muscle weakness in the progression of OA and pain.