The role of endogenous bone morphogenetic proteins in normal skeletal repair.

Abstract

Bone morphogenetic proteins play a key role in the regulation of the three major phases of fracture healing; the inflammatory response, the chondrogenic stage and the osteogenic stage. BMP-2 and 4 show a rapid response during the initial inflammatory stage, and BMP-2 has been shown to be essential for fracture healing to occur. BMP-2 and 4 are also present in the chondrogenic stage, although expression levels of BMP-3b (GDF10) and BMP-6 seemingly have specific peaks at day 7, suggesting a crucial role in this process. BMP-3, 4 and 5 are also abundantly present during this stage. In the osteogenic stage studies have shown that BMPs 1, 2, 3, 3b, 4, 5, 6, 7 and 8A have high levels of expression. It is important to note that of these, BMP-3 and 4 have a peak in their expression and BMP-7 and 8A are almost exclusively expressed during day 14 and 21. The expression of the different BMPs in these stages is believed to be orchestrated by autoregulatory activation between the BMPs, negative feed back loops and external antagonists. Alterations of the BMP signaling pathway, either by direct targeting of the BMPs or by their inhibitors has been shown to interfere with embryologic skeletal development and a post natal regenerative repair following skeletal trauma.