Osteoarthritis (OA) is a degenerative disease involving chondrocytes,
cartilage and other joint tissues, and has a number of
underlying causes, including both biochemical and mechanical
factors. Although proinflammatory factors including nitric oxide
(NO) are associated with OA, there is recent evidence suggesting
that NO and its redox derivatives may also play protective roles in
the joint. However, the mechanisms that underlie the development
and progression of OA are not completely understood. Experiments
have demonstrated that NO plays a catabolic role in the
development of OA and mediates the inflammatory response, is
involved in the degradation of matrix metalloproteinases, inhibits
the synthesis of both collagen and proteoglycans, and helps to
mediate apoptosis. However, there is also evidence that in cultured
chondrocytes the addition of exogenous NO may inhibit proinflammatory
activation by preventing the nuclear localization of the transcription
factor nuclear factor-κB, whereas the presence of
peroxynitrite - a redox derivative of NO - appears to enhance the
inflammatory response by sustaining the nuclear localization of
nuclear factor-κB. In addition, under some conditions exogenous
NO can stimulate collagen synthesis in cultured rat fibroblasts and
human tendon cells. The protective roles of NO in multiple cell
types, along with the opposing activities in cultured chondrocytes,
suggest that NO may play additional protective roles in
chondrocyte function. NO and its derivatives have a similarly
complicated involvement in nociception and pain, which may
contribute to the functional disability of OA. Further research may
help to elucidate a potential role for NO-donating agents in the
management of OA.
