Molecular mechanisms of cartilage destruction in osteoarthritis.


ing way to the concept of OA as an inflammatory form of arthritis where the inflammation is present at the molecular level within the articular cartilage. There is mounting evidence that the cartilage destruction in OA is the result of the activity of cytokines, chemokines, and other inflammatory mediators. These inflammatory factors are commonly produced by immune cells and synovial cells in the classic forms of inflammatory arthritis but in OA, they are produced by the chondrocytes. The inflammatory mediators produced by chondrocytes include cytokines and chemokines such as IL-1, IL-6, IL-7, IL8, IL-17, IL-18, MCP-1, LIF, GRO, and oncostatin M; reactive oxygen species such as nitric oxide, superoxide, hydrogen peroxide and peroxynitrite; and lipid-derived inflammatory mediators such as prostaglandins and leukotrienes. These mediators act in an autocrine and paracrine fashion to stimulate the chondrocyte to produce proteolytic enzymes, including aggrecanases and matrix metalloproteinases that contribute to destruction of the cartilage matrix. In addition to stimulating production of catabolic factors, the inflammatory mediators produced by chondrocytes also contribute to cartilage loss through the inhibition of matrix synthesis. As OA develops, the chondrocytes respond to the damage and loss of matrix by proliferating (resulting in the formation of chondrocyte clusters or "clones") and by attempting to produce matrix including production of matrix proteins more commonly found during development (such as type IIA procollagen). But an imbalance between synthesis and degradation is present resulting in net loss of matrix. The changes observed in OA may be due at least in part to a phenotypic switch where chondrocytes in the articular cartilage assume some of the characteristics of cells in the hypertrophic zone of the growth plate including production of type X collagen and the collagenase MMP-13. The initiators of the OA process are not entirely clear and most likely are multifactorial. Clearly, abnormal joint loading, due to altered biomechanics (from injury, congenital anatomic defects or obesity), is important, as are genetic factors and factors associated with aging. No matter the initiaJ Musculoskelet Neuronal Interact 2008; 8(4):303-306

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@article{Loeser2008MolecularMO, title={Molecular mechanisms of cartilage destruction in osteoarthritis.}, author={Richard F. Loeser}, journal={Journal of musculoskeletal & neuronal interactions}, year={2008}, volume={8 4}, pages={303-6} }