CARTILAGE-DERIVED MORPHOGENETIC PROTEINS AND OSTEOGENIC PROTEIN-1 DIFFERENTIALLY REGULATE OSTEOGENESIS

Cartilage-derived morphogenetic proteins-1 and -2 (CDMP-1 and CDMP-2) are members of the bone morphogenetic protein (BMP) family, which play important roles in embryonic skeletal development, We studied the bio logical activities of recombinant CDMP-1 and CDMP-2 in chondrogenic an d osteogenic differentiation and investigated their binding properties to type I and type II serine/threonine kinase receptors, In vivo, CDM P-1 and CDMP-2 were capable of inducing dose-dependently de novo carti lage and bone formation in an ectopic implantation assay, In vitro stu dies using primary chondrocyte cultures showed that both CDMP-1 and CD MP-2 stimulated equally de novo synthesis of proteoglycan aggrecan in a concentration-dependent manner. This activity was equipotent when co mpared with osteogenic protein-1 (OP-1), In contrast, CDMPs were less stimulatory than OP-1 in osteogenic differentiation as evaluated by al kaline phosphatase activity and expression levels of bone markers in A TDC5, ROB-C26, and MC3T3-E1 cells, CDMP-2,vas the least osteogenic in these assays, Receptor binding studies of CDMP-1 and CDMP-2 revealed t hat both have affinity for the BMP receptor type IB (BMPR-IB) and BMPR -II, and weakly for BMPR-IA, Moreover, using a promoter/reporter const ruct, transcriptional activation signal was transduced by BMPR-IB in t he presence of BMPR-II. upon CDMP-1 and CDMP-2 binding, Our data show that distinct members of the BMP family differentially regulate the pr ogression in the osteogenic lineage, and this may be due to their sele ctive affinity for specific receptor complexes.