The bone morphogenetic proteins antagonist noggin inhibits membranous ossification

Bone morphogenetic proteins (BMPs) are expressed and secreted during fractu re repair. Although they are likely to be required for this process, little is known about their physiological role in bone regeneration. Noggin is a protein that specifically binds and inactivates several BMPs, It plays fund amental roles during early embryonal development and limb morphogenesis by this BMP-inactivating activity. This study shows that Noggin can modify bon e formation in vivo in the adult animal and, thus, indirectly, that BMP sig naling is indispensable in this process. A noggin mutein (hNg Delta B2-Fc) engineered so as to display increased bioavailability was used. Bilateral t itanium bone chambers mere inserted in 70 rats, and side comparisons for bo ne formation in the chambers were done. The hNg Delta B2-Fc had no effect o n total amount of tissue formed in the chamber but decreased the amount of bone compared with both buffer controls and a control made up of an Fc-tagg ed IL-6R alpha protein, which had no effects of its own, Also, wild-type no ggin inhibited bone formation. Thus, endogenous BMP signaling is necessary for normal bone regeneration.