BoneKEy Reports | BoneKEy Watch

Treatment with a BMP receptor blocker increases bone mass in mice

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DOI:10.1038/bonekey.2012.179

The BMPR1A receptor binds bone morphogenetic proteins (BMPs) from the TGFβ superfamily. It is known that conditional deletion of this receptor in osteoblasts results in increased bone mass. This study investigated the therapeutic potential of mBMPR1A-mFc, a soluble fusion protein that blocks BMP2 and BMP4, inhibiting downstream signaling.

Both mature and immature mice treated with mBMPR1A-mFc showed a significant increase in trabecular bone volume, bone mineral density and other bone parameters as well a decrease in trabecular separation. Treatment of estrogen deficient mice also enhanced their bone mass and bone strength, restoring trabecular thickness, trabecular bone volume and cortical thickness to pre-ovariectomized levels.

At the molecular level, mBMPR1A-mFc appears to reduce expression of Dickkopf-1, which allows osteoblast expansion in the early stages. The number of osteoblasts then starts to fall, accompanied by a decrease in RANKL production, lower serum levels of tartrate-resistant acid phosphatase and enhanced expression of osteoprotegerin. The net effect is a higher rate of bone formation and a lower rate of bone resorption.

Editor's comment: Soluble BMPR1A may be another promising candidate treatment for bone loss disorders such as osteoporosis; its ability to reverse bone loss in ovariectomized mice is particularly promising.

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