OSCAR (osteoclast-associated Ig-like receptor) is a bone-specific regulator of osteoclastogenesis expressed on osteoclast precursors and chondrocytes. As a collagen receptor, OSCAR binds extracellular matrix collagen-II and functions as a signal transduction molecule critical for osteoclast differentiation 1. During bone remodeling, OSCAR expression on hematopoietic precursors facilitates their differentiation into osteoclasts through cell-cell contact with osteoblasts 1. Beyond skeletal homeostasis, OSCAR plays an unexpected role in osteoarthritis pathology. In articular chondrocytes, OSCAR mediates transcriptional repression of PPARγ, driving COX-2-related inflammation and cartilage degradation 2. Pharmacologically, 5-aminosalicylic acid competitively inhibits collagen-II binding to OSCAR, thereby reversing PPARγ repression and suppressing inflammation while promoting extracellular matrix anabolism and chondrogenesis 2. This OSCAR-mediated mechanism represents a disease-modifying therapeutic target: intra-articular 5-ASA administration ameliorated surgically-induced osteoarthritis in mice, even when administered after disease onset 2, suggesting OSCAR antagonism could provide disease-modifying benefits in osteoarthritis patients. OSCAR's dual role—supporting physiological bone remodeling while contributing to pathological joint destruction—highlights its clinical significance as both a regulatory node in skeletal biology and a therapeutic target for degenerative joint disease.