Pathogenesis of Osteoarthritis

Osteoarthritis (OA) is a disease of the entire joint, characterized by degradation of the articular cartilage, hypertrophy of bone at the margins (i.e., osteophytes), subchondral sclerosis, and a range of biochemical and morphologic alterations of the synovial membrane and joint capsule. Risk factors for developing OA include age, joint location, obesity, genetic predisposition, joint malalignment, trauma, and sex. Morphologic changes in early OA include articular cartilage surface irregularity, superficial clefts within the tissue, and altered proteoglycan distribution. Late OA changes include deepened clefts, increase in surface irregularities, and eventual articular cartilage ulceration, exposing the underlying bone. Chondrocytes form clusters or clones in an attempt at self-repair. The matrix metalloproteinase family of proteinases degrades proteoglycans (aggrecanases) and collagen (collagenases). Suboptimal repair response of normal articular cartilage to injury typically results in secondary OA. Chondrocytes sense and respond to mechanical and physicochemical stimuli via several regulatory pathways. Mediators classically associated with inflammation during the course of OA include IL-1β and tumor necrosis factor. Nitric oxide, produced by the inducible isoform of nitric oxide synthase, is a major catabolic factor produced by chondrocytes in response to pro-inflammatory cytokines. Expression of inducible cyclooxygenase-2 is increased in OA chondrocytes. Low-grade inflammation occurs in OA synovial tissue and contributes to disease pathogenesis.