Osteoarthritis: Epidemiology, Pathogenesis, and Treatment.

Osteoarthritis (OA) is the most common chronic joint disorder and a major cause of disability worldwide. Once regarded as a consequence of cartilage wear, OA is now recognized as a complex whole-joint disease involving coordinated pathological changes in articular cartilage, synovium, and subchondral bone. Disease progression is driven by chronic low-grade inflammation, metabolic dysregulation, oxidative stress, and abnormal cellular responses to mechanical stress. These processes are mediated by interconnected signaling networks that regulate inflammatory responses, extracellular matrix (ECM) metabolism, and tissue remodeling. Epigenetic mechanisms, such as DNA methylation, histone modifications, and noncoding RNAs, are increasingly recognized as regulators of OA-related gene expression. However, how signaling networks integrate with epigenetic regulation, particularly histone methylation, remains incompletely understood. In this review, we summarize the epidemiological burden and major risk factors of OA, describe pathological remodeling across joint tissues, and discuss key signaling pathways involved in OA pathogenesis before outlining epigenetic mechanisms. We also highlight the role of histone methylation in inflammation, metabolic imbalance, and tissue remodeling, and summarize current nonpharmacological, pharmacological, injectable, and surgical treatment strategies. Together, this review provides an integrated overview of the epidemiology, pathogenesis, and treatment of OA.