Potential crosstalk between ferroptosis and immunosenescence in osteoarthritis: evidence integration and translational insights from the osteoimmune microenvironment.

Osteoarthritis (OA) has traditionally been regarded as a degenerative disease primarily characterized by cartilage wear and tear. However, accumulating evidence suggests that it is fundamentally a whole-joint disorder involving the coordinated participation of cartilage, synovium, subchondral bone, and immune components. In recent years, ferroptosis and immunosenescence have each been recognized as contributors to OA initiation and progression, yet their potential interplay within the osteoimmune microenvironment remains insufficiently integrated. This review summarizes how iron homeostasis imbalance, lipid peroxidation, and impaired antioxidant defense promote ferroptosis in joint-resident cells, and how immunosenescence influences joint homeostasis through chronic low-grade inflammation and functional remodeling. It further analyzes the possible crosstalk between these two processes in cartilage, synovium, subchondral bone, and related immune cells. In addition, this review outlines current advances in therapeutic strategies, including anti-ferroptotic interventions, anti-senescence modulation, and optimization of local delivery approaches. At present, direct evidence supporting a stable causal loop between ferroptosis and immunosenescence in OA remains limited, and many of the proposed mechanisms are still largely derived from