Medicine and Health Sciences
Osteoporosis is a disease of low bone mineral density (BMD) that affects 10 million Americans with an additional 34 million at risk for developing the disease. Current FDA-approved therapies for osteoporosis involve anti-resorptive agents but many patients would benefit from augmenting bone formation as well as inhibiting bone loss. We recently reported that targeted deletion of the type 2 BMP receptor BMPR2 using Prx1-Cre in skeletal progenitor cells in mice leads to dramatically increased bone mass and bone formation rate by ten weeks of age in the absence of changes in osteoclast function (Lowery et al 2015). In the present study, we examined the age-related impact of Bmpr2 deletion and found that, consistent with our previous results, both male and female Bmpr2-cKO mice exhibit high bone mass when compared to control mice at 55 weeks of age. We also found that the age-related decline in bone mass from 15 weeks to 55 weeks of age in Bmpr2-cKO mice is reduced approximately three-fold compared to control mice, with male and female Bmpr2-cKO mice losing on average only 18% and 27%, respectively, while male and female control mice lost 55% and 77%, respectively, over the same time span. High bone mass in aged Bmpr2-cKO mice is associated with elevated serum levels of the bone formation marker Procollagen Type I N-terminal Propeptide (P1NP). In contrast, serum levels of the bone resorption marker Collagen Type I C-telopeptide (CTx) are unchanged in Bmpr2-cKO mice. Collectively, these findings indicate that loss of Bmpr2 in skeletal progenitor cells causes a sustained imbalance in bone formation vs. bone resorption and results in high bone mass in the aging skeleton. Our findings suggest that strategies aimed at controlling signaling through BMPR2 have the potential to impact bone mass in the aging adult skeleton.
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Eaton, Michael S.; Newby, Jordan B.; Hudnall, Aaron M.; Rosen, Vickie; and Lowery, Jonathan W. Ph.D., "Loss of BMPR2 Expression in Skeletal Progenitor Cells Reduces Age-Related Bone Loss" (2015). MU-COM Research Day. 1.