THE ROLE OF INFLAMMATION IN OSTEOARTHRITIS: PATHOGENIC MECHANISMS AND MODERN TREATMENT STRATEGIES

Abstract

Osteoarthritis (OA) has long been regarded as a passive, “wear-and-tear” degenerative disease of articular cartilage, but contemporary evidence reframes it as a low-grade chronic inflammatory disease affecting the whole joint organ — synovium, cartilage, and subchondral bone alike. This narrative review synthesizes current evidence on the inflammatory pathogenesis of OA and modern treatment strategies, drawing on the 2019 OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis and subsequent updates through 2025. Mechanical joint stress and chondrocyte senescence release damage-associated molecular patterns (DAMPs) that engage Toll-like receptors on synoviocytes and macrophages, activating NF-κB signaling and driving secretion of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). These cytokines induce chondrocyte expression of matrix metalloproteinase-13 (MMP-13) and ADAMTS-5, degrading type II collagen and aggrecan, while low-grade synovitis, subchondral bone remodeling, osteophyte formation, and neoangiogenesis with nerve ingrowth close a self-perpetuating whole-joint inflammatory cycle that sustains both structural progression and pain. Modern management remains predominantly symptomatic: core non-pharmacologic treatment (exercise, education, and weight management) underlies all care, topical and oral anti-inflammatory agents and intra-articular corticosteroids or hyaluronic acid provide symptom control, and emerging disease-modifying osteoarthritis drugs (DMOADs) targeting inflammatory and catabolic pathways remain investigational, with no agent yet approved for disease modification. A mechanism-based understanding of inflammation in OA, combined with individualized, comorbidity-informed non-surgical management and judicious use of surgery in advanced disease, is central to reducing pain and disability, including within the healthcare system of Uzbekistan.