Degradative and repair responses of cartilage to cytokines and growth factors occur via distinct pathways.

Cartilage destruction mediated by IL-1 is due to increased matrix lysis and decreased matrix repair. To determine whether the two processes are linked, we studied the influence of growth factors on IL-1 induced neutral protease induction, proteoglycan synthesis inhibition and IL-1 receptor expression. With respect to neutral protease induction, FGF and PDGF potentiated IL-1 activity, TGF-beta inhibited, while EGF, IGF-1 and -2 had no effect. With respect to IL-1 receptor expression, FGF and PDGF induced more IL-1 receptors, TGF-beta inhibited, while IGF-1, and 2 had no effect. Finally, with respect to proteoglycan synthesis, TGF-beta, PDGF and IGF-1 reversed IL-1 induced PG suppression to different extents, while FGF slightly potentiated IL-1 induced suppression of aggrecan synthesis. The results suggest that while IL-1 affects both increased aggrecan loss and decreased synthesis, the pathways leading to the effector functions are not necessarily linked and are likely to be distinct.