Stimulatory effects of cartilage-derived morphogenetic proteins 1 and 2 onosteogenic differentiation of bone marrow stromal cells

Cartilage-derived morphogenetic proteins 1 and 2 (CDMP-1 and CDMP-2) are me mbers of the bone morphogenetic protein (BMP) family which play an importan t role in embryonic skeletal development. Throughout adult life, bone marro w-derived precursor cells maintain their ability to differentiate into oste oblasts in response to local growth factors. This study examines the osteog enic potential of CDMP-1, CDMP-2, BMP-6 and osteogenic protein 1 (OP-l) in bone marrow stromal cells (BMSC) and investigates the endogenous expression of CDMPs/BMPs and their respective activin receptor-like kinase (ALK) rece ptors, A 4-day exposure of BMSC to CDMP-1, CDMP-2, BMP-6, and OP-1 under se rum-free conditions stimulated the progression of the osteogenic lineage in a dose-dependent manner as evaluated by alkaline phosphatase activity and osteocalcin synthesis, In contrast to the BMPs, CDMP-1 and especially CDMP- 2 were significantly less osteogenic, as confirmed by Northern blot analysi s. Moreover, BMSC were shown to express endogenously CDMP-2, BMP-2 to -6 an d ALK-1, -2, -3, -5 and -6, Phenotypic characterization of BMSC by RT-PCR s howed transcripts of the fat marker adipsin and the prechondrocytic marker procollagen type IIA; however, we were unable to detect the mature cartilag e markers, procollagen type IIB and aggrecan, even after growth factor trea tment. Our data indicate that CDMP-1, CDMP-2, BMP-6 and OP-l enhance the os teogenic phenotype in BMSC, with CDMPs being clearly less osteogenic than B MPs, The endogenous expression of a variety of CDMPs/BMPs and their respect ive ALK receptors, suggests a possible involvement of these growth factors in the osteogenic differentiation of bone marrow progenitor cells, (C) 2000 Academic Press.