Potential synergies between matrix proteins and soluble factors on resorption and proteinase activities of rabbit bone cells

Human growth hormone (GH) has recently been found to stimulate osteoclastic resorption, cysteine-proteinase and metalloproteinase activities (MMP-2 an d MMP-9) in vitro via insulin-like growth factor-I (IGF-I) produced by stro mal cells. The present study investigated the effects of two extracellular matrix components (vitronectin and type-I collagen) on hGH- and hIGF-1-stim ulated osteoclastic resorption and proteinase activities in a rabbit bone c ell model. After 4 days of rabbit bone cell culture on dentin slices with v itronectin coating, hGH and hIGF-1 stimulated bone resorption and hIGF-1 up modulated cysteine-proteinase activities. MMP-2 expression (but not resorpt ion, cathepsin or MMP-9 activities) was upmodulated by hGH and hIGF-1 on de ntin slices coated with type I collagen as compared to those without coatin g. Then, vitronectin was synergistic with hIGF-1 in the regulation of cyste ine-proteinase production whereas collagen showed synergy with hGH and hIGF -1 in the regulation of MMP-2 production. Anti-alphav beta3 totally abolish ed the effects of hGH and hIGF-1 on metalloproteinase release, but had no i nfluence on cathepsin release. The results suggest that cysteine-proteinase modulation is not mediated by alphav beta3 integrin (strongly expressed on osteoclastic surface) whereas the resorption process and metalloproteinase modulation are clearly mediated by this integrin. Our finding about the co llagen coating also suggests that hGH- and hIGF-1-stimulated MMP-2 activity are mediated, along with alphav beta3 integrin, by another adhesion molecu le.