Obesity-induced fibrosis in osteoarthritis: Pathogenesis, consequences and novel therapeutic opportunities

Osteoarthritis (OA) is a significant global burden, affecting more than half a billion people across the world. It is characterized by degeneration and loss of articular cartilage, synovial inflammation, and subchondral bone sclerosis, leading to pain and functional impairment. After age, obesity is a major modifiable risk factor for OA, and it has recently been identified as a chronic disease by the World Health Organization (WHO). Obesity is associated with high morbidity and mortality, imposing a significant cost on individuals and society. Obesity increases the risk of knee OA through increased joint loading, altered body composition, and elevated proinflammatory adipokines in the systemic circulation. Moreover, obesity triggers fibrotic processes in different organs and tissues, including those involved in OA. Fibrosis in OA refers to the abnormal accumulation of fibrous tissue within and around the joints. It can be driven by increased adiposity, low-grade inflammation, oxidative stress, and metabolic alterations. However, the clinical outcomes of fibrosis in OA are unclear. This review focuses on the link between obesity and OA, explores the mechanism of obesity-driven fibrosis, and examines potential therapeutic opportunities for targeting fibrotic processes in OA.