Osteoarthritis (OA) is the most common form of arthritis and the leading cause of chronic disability in adults, affecting over 300 million people worldwide. Once considered a simple 'wear and tear' disease, OA is now understood as a complex, multifactorial process involving active biochemical degradation of articular cartilage, subchondral bone remodeling, synovial inflammation, and ultimately, whole-joint failure. Normal Articular Cartilage Biology: Articular (hyaline) cartilage is a specialized connective tissue that covers the ends of bones in synovial joints, providing a near-frictionless surface for joint movement and distributing mechanical loads across the subchondral bone. The cartilage matrix is composed of: (1) type II collagen fibers (60% of dry weight) providing tensile strength; (2) aggrecan proteoglycans (30% of dry weight) — large molecules with glycosaminoglycan side chains (chondroitin sulfate and keratan sulfate) that attract and bind water through osmotic effects, giving cartilage its compressive resilience and ability to withstand loading forces; (3) water (65-80% of wet weight) — the high water content is critical for nutrient diffusion (cartilage is avascular) and load distribution. Chondrocytes are the sole cellular component of cartilage, comprising...