Bone morphogenetic protein-7 selectively enhances mechanically induced bone formation

Abstract

The responses of bone cells to skeletal loading are clearly an important factor in bone biology, but much remains to be learned about the role of these responses in skeletal development, maintenance, and tissue repair. Bone morphogenetic proteins (BMPs) are key regulators of bone formation. We examined the effect of BMP-7 on periosteal and endosteal bone formation in response to increased mechanical loading using the rat tibial bending model. Female Sprague-Dawley rats were divided into four groups of six rats each. Three groups received four point bending loading at 60 N force; the fourth group received sham loading at the same force. The right tibia received 36 cycles of loading on Monday, Wednesday, and Friday for 2 weeks; the left tibia served as a nonloaded control. Just prior to loading, the three loaded groups were injected intraperitoneally with vehicle only or 10 μg/kg or 100 μg/kg of recombinant human BMP-7. Half the sham group received vehicle, and half were given 100 μg/kg of BMP-7. Bone forming surfaces were labeled twice in vivo with calcein, and histomorphometry was performed to quantify periosteal and endosteal bone formation in the loaded and control tibiae. BMP-7 had no effect on periosteal or endosteal bone formation in control or sham-loaded tibiae. Loading produced significantly more woven bone on the periosteal surface than sham loading, but BMP-7 treatment had no effect on this response. Endosteal bone formation was entirely lamellar, and loading (but not sham loading) increased the endosteal mineral apposition and bone formation rates. The higher BMP-7 dose more than doubled the load-induced increase in endosteal lamellar bone formation rate, primarily by increasing the amount of bone forming surface.