Abstract
Bone Morphogenetic Protein 7 (BMP7) is a powerful osteoinductive substance that could stimulate bone formation in difficult conditions including distraction osteogenesis. However, to be effective, large unphysiological doses are required. Blocking the expression of BMP antagonists could amplify the effects of BMP7, allowing smaller doses of BMP7 to be used without altering its osteogenic potential. In this study, BMP7 antagonist Noggin was shown to be upregulated following BMP7 injection in a rabbit distraction osteogenesis model suggesting a role for Noggin in controlling BMP7 activity. Blocking Noggin expression may thus permit smaller doses of BMP7 to be used effectively.
Distraction osteogenesis (DO) is an excellent method to form new bone. However, the long duration the external fixator has to be kept on until the new bone consolidates, could lead to numerous problems. BMP7 may accelerate bone formation in DO. However, large doses of BMP7 may be necessary. In this study, we investigated the expression of BMP7 antagonist Noggin in DO.
Noggin may control BMP7 activity through a negative feedback mechanism. Blocking Noggin may amplify the effects of BMP7, thus permitting the use of smaller doses of BMP7 effectively in DO.
Using smaller doses of BMP7 – while maintaining its powerful effects – may decrease side effects and render this drug more affordable economically.
Noggin is normally expressed in DO. Its expression is upregulated by local application of BMP7. Its expression is co-localized to the same cells that express BMP7 and its receptors.
The right tibia of sixteen rabbits was lengthened using a uniplanar fixator. The rabbits were divided into two groups: one received seventy-five micrograms recombinant BMP7 and the other placebo. All injections were performed one week after start of distraction. Rabbits were sacrificed ten minutes, one day, two days and two weeks following the injections. The expression of Noggin was studied in the distracted tissue by immunohistochemistry.
Noggin may play a role in DO. Blocking its action may have huge clinical implications, by permitting the use of smaller – but equally effective – amounts of BMP7.
Funding: CIHR, FRSQ and Shriners of North America
Correspondence should be addressed to Cynthia Vezina, Communications Manager, COA, 4150-360 Ste. Catherine St. West, Westmount, QC H3Z 2Y5, Canada
