Changes in Mouse Skeletal Progenitor Cells in a Model of Osteoporosis.
Tom Andrew, MBChB, MSc1, Danielle Struck, BS1, Michael Lopez, BS1, Tatiana Boyko, MD1, Michael Longaker, MD1, Charles Chan, BS PhD1, George Yang, MD PhD1,2.
1Stanford University, Palo Alto, CA, USA, 2Palo Alto VA Health Care System, Palo Alto, CA, USA.
PURPOSE- Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue. People with osteoporosis are more prone to fracture due to the decrease in bone mass with 40% of post-menopausal women developing an osteoporotic fracture. Of those suffering a fracture, 20% will die and only 30% will fully recover indicating that there is also a deficit in fracture healing. Our group recently described mouse skeletal progenitor cells. One sub-population, the mouse skeletal stem cell (mSSC) has been shown to be capable of forming all components of the skeleton. Another sub-population, the bone cartilage skeletal progenitor (BCSP) has been found to be important in fracture healing. We hypothesized that the changes in skeletal anatomy following estrogen depletion will be reflected by alterations in skeletal progenitor cell populations. METHODS- C57/BL6 mice underwent either sham operation or oophorectomy. Bone mineral density (BMD) was assessed by microCT. For fracture healing, mice underwent femur fracture 10 weeks after oophorectomy. Skeletal progenitor cells were harvested from uninjured bone or fracture callus as previously described and sorted by FACS. For colony forming units (CFUs), sorted cells were placed in growth medium for two weeks prior to colony counting. RESULTS- We first examined the impact of oophorectomy on BMD. 10 weeks after oophorectomy, mice were examined by microCT and BMD calculated from the femur. As expected, there was a significant decrease in BMD following oophorectomy compared to sham. Analysis of skeletal progenitors from uninjured bone showed significantly fewer mSSCs with decreased CFUs in oophorectomized versus sham. Following fracture, there was visibly less callus formed at the fracture site. Following fracture in oophorectomized mice, there was some increase in BCSPs in response, but it was nearly an order of magnitude less than seen in sham. CONCLUSIONS- Osteoporosis is a disease that can have devastating consequences for the health of older women. Our aging population will only increase the demand for viable therapies for the consequences of osteoporosis. While the impact of estrogen depletion on bone are well-characterized, it has not been very well understood at the cellular level. Here, we show the impact of oophorectomy on an important cellular component of the skeleton, and propose that therapies targeted at this cell population may be effective in combatting the disease. <!--EndFragment-->
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