Development of a therapeutic method of bone repair using BMP responding mesencbymal cells

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In 1971, Urist gave name bone morphogenetic protein (BMP) for the protein which was extracted from demineralized bone matrix with bloactivity inducing ectopic bone formation. This indicates that osteoprogenitor cells, which can differentiate into osteoblasts in response to BMP, are present in muscle and subcutaneous tissue. Human BMP cDNAs were first cloned in 1988, and over 15 cDNAs encoding BMPs have been cloned at present. Recently BMP receptors have also cloned. We have investigated the role of BMP-2 in regulation of differentiation of skeletal mesenchymal cells. In the present study, we conducted several experiments to develop a novel therapeutic method of bone repair, and obtained the following results.1) We confirmed the expression of BMP receptors (IA, IB and II) in primary rat osteoblastic cells by in situ hybridization and immunohistochemistry.2) We investigated the effect of BMP-2 on osteoblast differentiation using various culture cells, and demonstrated that the effects of BMP-2 varied among cell types used.3) We demonstarted that BMP-2 induced osteoblast differentiation in human muscles and skin fibroblasts.4) We transplanted BMP-2IPGS complex with osteoprogenitor cells into bone defects. This method generated new bone more effectively than that simply transplanted BMP-2IPGS.5) We triad to make antibodies against BMP receptor IA, but could not obtain neutralizing antibodies.