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.
Chandrasekhar
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Skeletal Diseases Research, Lilly Research Laboratories, Indianapolis, IN 46285.
Harvey
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Stack
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D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D010450:Endopeptidases / Q000096:biosynthesis; D006133:Growth Substances / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes
D016207:Cytokines; D006133:Growth Substances; D007375:Interleukin-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D013431:Sulfates; D013462:Sulfur Radioisotopes; D010450:Endopeptidases