CLONING AND CHARACTERIZATION OF A NOVEL MEMBER OF THE TRANSFORMING GROWTH FACTOR-BETA BONE MORPHOGENETIC PROTEIN FAMILY/

Members of the transforming growth factor-beta (TGF-beta) superfamily of growth and differentiation factors have been identified in a wide v ariety of organisms, ranging from invertebrates to mammals. Bone morph ogenetic proteins (BMPs) constitute a subgroup of proteins belonging t o the TGF-beta superfamily, BMPs were initially identified by their ab ility to induce endochondral bone formation at ectopic sites, suggesti ng a critical role for this family in development and regeneration of the skeleton. They are also expressed at a variety of nonskeletal site s during development, suggesting possible extraskeletal roles for thes e proteins. We cloned a novel member of the BMP family that is express ed at high levels in the placenta and the prostate and that we have de signated as prostate-derived factor (PDF), Based on cDNA sequence anal ysis, the predicted PDF protein contains two cysteines in addition to the seven conserved cysteines that are the hallmark of the members of the TGF-beta superfamily, In addition, Northern blot hybridization to poly(A)(+) RNA showed low levels of expression in the kidney and pancr eas. We further characterized the expression of this member of the BMP family by in situ. hybridization and immunohistochemistry. These resu lts show high expression in the terminal villae of the placenta. The e xpression of the protein as visualized by immunohistochemistry shows a n expression pattern identical to that of the message in the terminal villae of the placenta. In day 18 rat embryos, protein expression was also seen in the skin and in the cartilaginous tissue of developing sk eleton. Orchidectomy and dihydrotestosterone treatment of rats reveale d that PDF expression is regulated by androgens in the prostate. In ad dition, subcutaneous implantation of recombinant PDF induced cartilage formation and the early stages of endochondral bone formation. These data indicate that PDF has a functional relationship to the BMPs.