Osteoarthritis (OA) is a progressive joint disease characterized by varying degrees of pain and degeneration. The disease affects the structural and functional integrity of articular cartilage—the thin load-bearing tissue lining the ends of long bones—as well as the adjacent bone and other joint tissues. The clinical symptoms of OA include joint pain, stiffness, and swelling, which may lead to muscle weakness and impaired physical function. OA is generally diagnosed radiographically by bony changes, including osteophyte formation, cysts, subchondral sclerosis, and joint space narrowing. These clinical and radiographic features, which can often manifest independent of each other, are most commonly diagnosed in the knee, hip, and hand joints. Elderly individuals are most at risk for OA, and the incidence of OA increases significantly with age. Other risk factors include joint trauma, body mass index (ie, obesity), and heritable genetic factors. Of all joint diseases, OA is the most common, affecting an estimated 15% of the US population (5). Under normal physiological conditions, articular cartilage provides a nearly frictionless surface for the transmission and distribution of joint loads, exhibiting little or no wear over decades of use (9). This remarkable function is determined by the structure and composition of the extracellular matrix (ECM), which is primarily water. The remaining solid matrix is largely composed of a crosslinked network of collagen (mainly type II) and proteoglycans such as aggrecan (Fig. 1). Osteoarthritis is characterized by an imbalance between the anabolic and catabolic activities of the cartilage cell population, the chondrocytes, suggesting that alterations in cellular metabolism contribute to the onset and progression of the disease (6). Chondrocytes regulate their metabolic activity in response to mechanical, chemical, or electrical signals in their local microenvironment. In doing so, articular cartilage can alter its structure and composition to accommodate the physical demands of the body. Adult articular cartilage has a limited ability for self-repair, because the tissue is avascular, aneural, alymphatic, and sparsely populated by cells. Nevertheless, the components of the ECM are in a state of slow turnover, maintained in homeostatic balance by the catabolic and anabolic events of the chondrocytes. These activities are controlled through the processing of both genetic and environmental information (eg, growth factors, cytokines, and ECM composition). In particular, recent studies have shown that the mechanical stress environment of the joint is an important factor that influences (and presumably regulates) the activity of the chondrocytes in vivo (8).