First Author | Celeste AJ | Year | 1994 |
Journal | J Bone Miner Res | Volume | Suppl |
Pages | S136 (Abstr. 64) | Mgi Jnum | J:48647 |
Mgi Id | MGI:1274809 | Citation | Celeste AJ, et al. (1994) Bone morphogenetic protein-9, a new member of the TGF-beta superfamily. J Bone Miner Res Suppl:S136 (Abstr. 64) |
abstractText | Full text of Abstract. BONE MORPHOGENETIC PROTEIN-9, A NEW MEMBER OF THE TGF-Beta SUPERFAMILY. A.J. Celeste*, J.J. Song*, K. Cox, V. Rosen, and J.M.Wozney, Genetics Institute, Inc., Cambridge, MA 02140. Bone Morphogenetic Proteins (BMPs) are members of the TGF-Beta superfamily of growth and differentiation factors, and have been shown to play major roles in a variety of developmental processes. To date, eight members of the BMP family have been cloned, along with a number of related proteins within the TGF-Beta superfamily. Here we describe the molecular cloning and biological activity of a new member of the BMP family, BMP-9. A DNA fragment encoding the mature region of human BMP-4 was utilized to identify BMP-9 clones from a mouse liver cDNA library. BMP-9 amino acid sequence indicates that this protein is most closely related to Dorsalin-1, a BMP-like protein cloned drom embryonic chick. BMP-9 exhibits 80% homology to chick Dorsalin-1 and 30-35% homology to BMPs 2, 4, 5, 6, 7 and 8 at the amino acid level. Since the BMP family has been characterized by the ability of individual members to induce osteogenesis, we tested the activity of purified recombinant human BMP-9 (rhBMP-9) for osteogenic potential. In vitro, rhBMP-9 stimulated alkaline phosphatase activity in the osteoprogenitor cell line, W-20-17, in a dose responsive manner with an ED50 of 4 ng/ml. In vivo, only high doses of rhBMP-9 induced ectopic bone formation, with 25 ug/implant of rhBMP-9 needed to induce cartilage and bone tissue after 10 days of implantation. These results suggest that the primary function of BMP-9 may not be in osteogenesis, and we postulate that this new member of the TGF-Beta superfamily may function as a growth or differentiation factor primarily at nonskeletal sites. |