Identification of a key residue mediating bone morphogenetic protein (BMP)-6 resistance to noggin inhibition allows for engineered BMPs with superior agonist activity.

ABSTRACT: Bone morphogenetic proteins (BMPs) are used clinically to induce new bone formation in spinal fusions and long bone non-union fractures. However, large amounts of BMPs are needed to achieve these effects. BMPs were found to increase the expression of antagonists, which potentially limit their therapeutic efficacy. However, the relative susceptibility of osteoinductive BMPs to different antagonists is not well characterized. Here we show that BMP-6 is more resistant to noggin inhibition and more potent in promoting osteoblast differentiation in vitro and inducing bone regeneration in vivo when compared with its closely related BMP-7 paralog. Noggin was found to play a critical role as a negative feedback regulator of BMP-7 but not BMP-6-induced biological responses. Using BMP-6/7 chimeras,

SUBMITTER: Song K 

PROVIDER: S-EPMC2852956 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature