Regulatory Mechanisms of Interleukin-1 and its Targeted Therapeutic Strategies in Osteoarthritis: An Updated Review

Osteoarthritis (OA) is a prevalent degenerative joint disease and a leading cause of chronic pain and disability in the aging global population. Its pathogenesis is characterized by progressive articular cartilage degeneration, concomitant synovial inflammation, and aberrant subchondral bone remodeling. While the precise etiology is multifactorial and not fully elucidated, chronic, low-grade inflammation is recognized as a critical driver of disease progression. This inflammatory milieu disrupts the homeostatic balance between anabolic and catabolic processes in joint tissue. A complex network of cytokines and chemokines sustains this pathological state, with interleukin-1 (IL-1) emerging as a pivotal mediator. IL-1, particularly IL-1β, exerts potent catabolic effects by promoting the expression of matrix-degrading enzymes (e.g., MMPs, ADAMTS) while simultaneously suppressing the synthesis of essential extracellular matrix components, such as type II collagen and aggrecan. This dual action accelerates cartilage breakdown and undermines its repair capacity, identifying IL-1 signaling as a promising but clinically limited therapeutic target. This review details the central role of IL-1 in OA pathophysiology and dissects its key downstream signaling pathways, including NF-κB and MAPK activation. Furthermore, it provides a comprehensive summary and critical appraisal of current and emerging therapeutic strategies targeting the IL-1 pathway, evaluating their potential to modify disease progression and alleviate symptoms.