Mechanism Of Bone Formation Regulated By BMP9

Bone regeneration is critical to the effective management of many bone and musculoskeletal disorders, such as fracture healing and spinal fusion. Within series of stimulating factors, the more attention has been focused on the BMPs family. BMPs belong to the TGFb superfamily, and play an important role in embryonic development and bone formation. At least 15 types of BMPs have been identified in humans. Although several bone morphogenetic proteins (BMPs) (mostly BMP-2 and BMP-7) have been shown to induce bone formation, it is unclear whether the currently used BMPs represent the most osteogenic ones. Until recently, comprehensive analysis of osteogenic activity of all BMPs has been hampered by the fact that recombinant proteins are either not biologically active or not available for all BMPs. In this study, we used recombinant adenoviruses expressing the 14 types of BMPs (AdBMPs), and demonstrated that, in addition to currently used BMP-2 and BMP-7, BMP-9 effectively induced orthotopic ossification when AdBMP-transduced osteoblast progenitors were injected into the quadriceps of athymic mice. We confirmed it on a further study by a rabbit bone fracture modle. BMP-3, a negative regulator of bone formation, was shown to effectively inhibit orthotopic ossification induced by BMP-2 and BMP-7. However, BMP-3 exerted no inhibitory effect on BMP-9-induced bone formation, suggesting that BMP-9 may transduce osteogenic signaling differently , and it has been confirmed by gene chip, real time PCR and western blot. Our study expanded the research field of BMP signaling pathway , further more, the use of BMP9 would open a new door for bone regeneration in musculoskeletal disorders.