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New bone induction by rh-BMP-2 in immunodeficient mice

Bone morphogenetic protein-2 (BMP-2, a member of the BMP family and a larger TGFbeta superfamily, can induce endochondral bone formation in exstraskeletal sites. When implanted subcutaneously or intramuscularly, BMPs induce the developmentaL cascade of mesenchymal cells proliferation, cartilage differentiation, bone marrow invasion and final differentiation of bone cells in a well formed ossicle, The immunological phenomena of new bone induction are poorly defined in vivo, but it has been shown that femtomolar concentration of BMP-2 induced migration of macrophaes/monocytes in vitro. We studied bone induction by rhBMP-2 in mice lacking some parts of the immune response. Ten micrograms of rhBMP-2 were implanted subcutaneously in coagulated blood as a carrier in mice with the beta2 microglobulin (beta2m) or TNFR55 gene knockout. Ossicles were harvested on 3, 6, 9 and 12 days after implantation and morphologically analyzed. While mice homozygous for betam gene knockout had the time course of new bone induction similar to that of heterozgous littermates, mice homozygous for the TNFR55 knockout showed slower endochondral bone formation in comaparation to their heterozygous littermates. These results indicate that TNF could play an important role in new bone induction by BMPs.

bone morphogenetic proteins; bone induction; immune system

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