Implications of Mechanosensitive Ion Channels in the Pathogenesis of Osteoarthritis: A Comprehensive Review

Yuelong ZhangHuangming ZhuangXunshan RenPanghu Zhou^*

• Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China

Osteoarthritis (OA) is the predominant cause of joint pain and limited mobility in older people, and its prevalence is increasing as the population ages. Given the lack of effective therapeutic interventions, the disability rate associated with OA is a staggering 53%, which significantly affects the well-being of those affected and represents a significant social and family financial burden. Consequently, OA has emerged as a pressing social and public health concern globally. Various forms of mechanical strain, such as dynamic compression, fluid shear, tissue shear, and hydrostatic pressure, serve as crucial physical stimuli perceived by chondrocytes. Recent studies indicate that aberrant mechanical loading represents a fundamental risk factor for OA. Upon exposure to mechanical loading, chondrocytes translate mechanical cues into chemical signals primarily via mechanosensitive ion channels, resulting in alterations in cartilage metabolism. Numerous studies have demonstrated the significance of mechanosensitive ion channels in the pathogenesis of OA, suggesting that therapeutic interventions targeting these channels on chondrocytes may offer potential benefits. This review consolidates existing research on mechanosensitive ion channels in OA, offering insights into potential diagnostic and therapeutic strategies for the disease.Osteoarthritis (OA) is the most common degenerative joint disease that impacts over 500 million individuals globally and stands as a primary contributor to motor impairment in the older section of the population 1 . The key pathological characteristics of OA include cartilage degradation, synovial inflammation, subchondral bone restructuring, and osteophyte formation, resulting in symptoms such as joint pain, stiffness, motor impairment, and potential disability 2, 3 . For people with advanced or end-stage OA, the need for an artificial joint replacement places a considerable financial burden on society and families 4 . Currently, there remains a lack of efficacious pharmaceutical interventions to halt or reverse the advancement of OA. Clinical guidelines advocate the use of pharmacologic treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs), hyaluronic acid, and platelet-rich plasma primarily for pain management and enhancing quality of life, with limited impact on the deceleration of OA progression 5, 6 .