The research plan is to characterize the role of vg-1 related protein (vgr-1) in chondrogenesis and osteogenesis. This TGF-beta superfamily member has been localized to hypertrophic cartilage, but nothing is currently known about its function. Our hypothesis is that this protein either enhances differentiation of hypertrophic chondrocytes or promotes osteoblast formation, and that it must be expressed at a specific time and place for normal endochondral bone formation to occur. To test these ideas, we will assess the consequences of over-expression and abolished expression of vgr-1 protein in two different model systems: 1) two different pluripotent mesenchymal cell lines, and 2) a mandibular organ explant derived from the first branchial arch of murine embryos. These studies will determine if vgr-1 is both sufficient and necessary for chondrocytic or osteoblastic differentiation, and if disruption of its normal expression pattern still allows such differentiation processes to occur. These experiments will enhance our understanding of local factors that mediate endochondral bone formation, and may ultimately contribute to the management of growth disorders, metabolic bone diseases, and fracture healing.
| Perr, H A; Ye, J; Gitelman, S E (1999) Smooth muscle expresses bone morphogenetic protein (Vgr-1/BMP-6) in human fetal intestine. Biol Neonate 75:210-4 |
| Gitelman, S E; Kobrin, M; Lee, A et al. (1997) Structure and sequence of the mouse Bmp6 gene. Mamm Genome 8:212-4 |
| Silverman, L A; Gitelman, S E (1996) Immunoreactive inhibin, mullerian inhibitory substance, and activin as biochemical markers for juvenile granulosa cell tumors. J Pediatr 129:918-21 |
| Gitelman, S E; Kobrin, M S; Ye, J Q et al. (1994) Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo. J Cell Biol 126:1595-609 |
