A TGF-beta-inducible cell adhesion molecule, beta ig-h3, is downregulated in melorheostosis and involved in osteogenesis

Melorheostosis is a rare bone disease characterized by linear hyperostosis and associated soft tissue abnormalities. The skin overlying the involved b one lesion is often tense, shiny, erythematous, and scleodermatous. In orde r to look for genes differentially expressed between the normal and involve d skin, we cultured skin fibroblasts from the skin lesions of several affli cted patients, and identified differentially expressed genes by reverse dot -blot hybridization. We found that the genes human TGF-beta-induced gene pr oduct (beta ig-h3), osteoblast-specific factor 2, osteonectin, fibronectin, and type I collagen were all downregulated in the affected skin fibroblast s, with beta ig-h3 the most significantly affected. The expression of beta ig-h3 was induced by TGF-beta in both affected and normal fibroblasts. in a n effort to determine the mechanism of bone and skin abnormalities in melor heostosis, we made recombinant beta ig-h3. Both immobilized and soluble rec ombinant beta ig-h3 proteins with or without an RGD motif inhibited bone no dule formation of osteoblasts in vitro. Taken together, our results suggest that altered expression of several adhesion proteins may contribute to the development of hyperostosis and concomitant soft tissue abnormalities of m elorheostosis, with beta ig-h3 in particular playing an important role in o steogenesis. (C) 2000 Wiley-Liss, Inc.