CARTILAGE-DERIVED MORPHOGENETIC PROTEINS - NEW MEMBERS OF THE TRANSFORMING GROWTH-FACTOR-BETA SUPERFAMILY PREDOMINANTLY EXPRESSED IN LONG BONES DURING HUMAN EMBRYONIC-DEVELOPMENT

Partially purified extracts from newborn calf articular cartilage were found to induce cartilage and bone when subcutaneously implanted in r ats. This activity showed characteristics of bone morphogenetic protei ns (BMPs). Degenerate oligonucleotide primer sets derived from the hig hly conserved carboxyl-terminal region of the BMP family were designed and used in reverse transcription-polymerase chain reactions with pol y(A)(+) RNA from articular cartilage as template to determine which BM Ps are produced by chondrocytes. Two novel members of the transforming growth factor-beta (TGF-beta) superfamily were identified and designa ted cartilage-derived morphogenetic protein-1 (CDMP-1) and -2 (CDMP-2) . Their carboxyl-terminal TGF-beta domains are 82% identical, thus def ining a novel subfamily most closely related to BMP-B, BMP-6, and oste ogenic protein-1. Northern analyses showed that both genes are predomi nantly expressed in cartilaginous tissues. In situ hybridization and i mmunostaining of sections from human embryos showed that CDMP-1 was pr edominantly found at the stage of precartilaginous mesenchymal condens ation and throughout the cartilaginous cores of the developing long bo nes, whereas CDMP-2 expression was restricted to the hypertrophic chon drocytes of ossifying long bone centers. Neither gene was detectable i n the axial skeleton during human embryonic development. The cartilage -specific localization pattern of these novel TGF-beta superfamily mem bers, which contrasts with the more ubiquitous presence of other BMP f amily members, suggests a potential role for these proteins in chondro cyte differentiation and growth of long bones.