Growth/differentiation factor-5 induces angiogenesis in vivo.

Bone morphogenetic proteins (BMPs) are multifunctional cytokines, which induce bone and cartilage formation and exert various other effects on many tissues. Since angiogenesis is involved in the bone formation process, certain members in the BMP family may induce angiogenesis. We examined the in vivo angiogenic activity of BMP family members, i.e., growth/differentiation factor (GDF)-5 and BMP-2. GDF-5 induced angiogenesis in both chick chorioallantoic membrane and rabbit cornea assays. In contrast, BMP-2 did not induce angiogenesis. In order to elucidate the mechanism of angiogenesis, we examined the effects of GDF-5 on cultured bovine aortic endothelial cells (BECs). GDF-5 induced plasminogen activator activity and accelerated the migration of BECs in a chemotactic fashion, which may contribute to the process of angiogenesis in vivo. These results suggest that GDF-5 is one of the molecules which induce angiogenesis in the bone formation process.