Nitric oxide alters chondrocyte function by disrupting cytoskeletal signaling complexes

Components of osteoarthritis include increases in pericellular fibronectin and in chondrocyte beta1 integrin expression. Events which follow ligation of fibronectin to its chondrocyte-receptor, the integrin alpha5beta1 include an assembly of a subplasmalemmal actin/rho A/focal adhesion kinase signaling complex. In addition, nitric oxide (NO), a potential mediator of cartilage pathophysiology disrupts the cytoskeletal signaling complex associated with integrin signaling. In these studies, we examined the relationship among integrin signaling, biosynthesis of S-35 sulfate containing proteoglycans and release of YKL-40 (a secretory glycoprotein) by comparing cell responses using cells plated on a fibronectin-coated or polyHEME coated surfaces. We report that the release of proteoglycan and glycoprotein require anchorage dependent signals by integrin costimulation. NO which disrupts the integrin signaling complex attenuates both cell responses. Taken together NO may serve as a nonspecific 'brake' to prevent anabolic and catabolic injury responses.