Loss of BMPR2 Expression in Skeletal Progenitor Cells Reduces Age-Related Bone Loss
Medicine and Health Sciences
Osteoporosis is a disease of low bone mineral density that affects 10 million Americans and accounts for 1.5 million fractures annually. With an additional 34 million Americans at risk for developing the disease, osteoporosis is both a significant health problem and a considerable socioeconomic burden. Current first-line therapies 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 in skeletal progenitor cells of the limb bud using Prx1-Cre (Bmpr2-cKO mice) leads to dramatically increased bone mass and bone formation rate by ten weeks of age in the absence of changes in osteoclast number or function (Lowery et al 2015). In the present study, we examined the impact of Bmpr2 deletion on age-related bone loss in Bmpr2-cKO mice. Consistent with our previous results, 55-week-old female Bmpr2-cKO mice exhibit approximately four-fold higher bone mass in the tibia than control mice. Moreover, the age-related decline in bone mass from 15 weeks to 55 weeks of age in female Bmpr2-cKO mice is reduced approximately twofold compared to control mice. Bone mass of the L5 vertebrae, which is outside the Prx1-Cre expression domain, is unchanged in Bmpr2-cKO mice compared to control mice at all ages examined. Quantification of the serum bone turnover markers Procollagen Type I N-terminal Propeptide (PINP) and Collagen Type I C-telopeptide (CTx) suggest that high bone mass in aging female Bmpr2-cKO mice is preserved due to a sustained increase in bone formation rate to at least 35 weeks of age with no alteration in bone resorption. Collectively, our findings provide insight into the mechanisms regulating age-related bone loss and 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. OMSIII, "Loss of BMPR2 Expression in Skeletal Progenitor Cells Reduces Age-Related Bone Loss" (2016). MU-COM Research Day. 37.