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

A.V. Rousselle1, C. Damiens1, E. Grimaud1, Y. Fortun1, M. Padrines1, N. Passuti2 and D. Heymann1,3

1EE 99-01, Laboratory of Physiopathology of Bone Resorption, Faculty of Medicine, Nantes, 2Department of Orthopaedic Surgery, Nantes Hospital, Nantes, France and 3Laboratory of Histology and Embryology, Medicine Faculty, Nantes, France

Offprint requests to: Dr. D. Heymann, EE 99-01, Laboratory of Physiopathology of Bone Resorption, Medicine Faculty, 1 rue Gaston Veil, 44035 Nantes cedex 1, France. Fax: +33 (2) 41 28 49. e-mail: dominique.heymann@sante.univ-nantes.fr

Summary. Human growth hormone (GH) has recently been found to stimulate osteoclastic resorption, cysteine-proteinase and metalloproteinase activities (MMP-2 and MMP-9) in vitro via insulin-like growth factor-I (IGF-I) produced by stromal cells. The present study investigated the effects of two extracellular matrix components (vitronectin and type-I collagen) on hGH- and hIGF-1-stimulated osteoclastic resorption and proteinase activities in a rabbit bone cell model. After 4 days of rabbit bone cell culture on dentin slices with vitronectin coating, hGH and hIGF-1 stimulated bone resorption and hIGF-1 upmodulated cysteine-proteinase activities. MMP-2 expression (but not resorption, cathepsin or MMP-9 activities) was upmodulated by hGH and hIGF-1 on dentin slices coated with type I collagen as compared to those without coating. Then, vitronectin was synergistic with hIGF-1 in the regulation of cysteine-proteinase production whereas collagen showed synergy with hGH and hIGF-1 in the regulation of MMP-2 production. Anti-avß3 totally abolished the effects of hGH and hIGF-1 on metalloproteinase release, but had no influence on cathepsin release. The results suggest that cysteine-proteinase modulation is not mediated by avß3 integrin (strongly expressed on osteoclastic surface) whereas the resorption process and metalloproteinase modulation are clearly mediated by this integrin. Our finding about the collagen coating also suggests that hGH- and hIGF-1-stimulated MMP-2 activity are mediated, along with avß3 integrin, by another adhesion molecule. Histol. Histopathol. 16, 727-734 (2001)

Key words: Osteoclast, Resorption, Proteinase, Vitronectin, Collagen

DOI: 10.14670/HH-16.727