The primary goals of the Cellular Biochemistry Group are to determine the composition and functional features of the supramolecular complex of proteins that calcifies, and how cells regulate this process. Towards these aims, cell cultures that support and form mineralized tissues were established for biochemical analysis, and for studies at the genomic level in collaboration with Drs. Marian F. Young and Larry W. Fisher. Studies were initiated to characterize the biosynthetic products of a cell line BBE (bovine bone endothelial cells) since the vasculature has been shown to influence bone metabolism. It was found that these cells synthesize fibronectin, type I collagen, osteonectin and thrombospondin, and induce the preosteoclastic cell line, FLG 29.1, to attach and multinucleate. Further characterization of FLG 29.1 also indicated that they synthesize bone sialoprotein, as has been observed in bona fide osteoclasts by in situ hybridization and immunohistochemistry. Continued analysis of cell- matrix interactions indicate that the two small proteoglycans found in bone, biglycan and decorin, inhibit bone cell attachment to some but not all RGD-containing proteins, suggesting that osteoblastic cells can modulate their attachment to the surrounding environment by the production of such inhibitory molecules. Cell attachment to bone matrix proteins was also found to depend on the phenotypic traits and maturational stage of cloned mouse marrow stromal fibroblasts. Lastly, studies utilizing bone- forming cultures from patients with different forms of osteogenesis imperfecta indicates that there is a major change in the stoichiometry of extracellular matrix proteins, irrespective of the detectability of a collagen mutation. While synthesis of versican, biglycan, decorin and osteonectin are decreased, thrombospondin and fibronectin are increased. These changes may contribute significantly to cell-matrix interactions and may play a role in the pathophysiology of this brittle bone disease.
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