Maximizing PTH Anabolic Osteoporosis Therapy. Revision
Technical Report,15 Aug 2015,14 Aug 2016
Trustees of Indiana University Indianapolis United States
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The purpose of this study is to test the efficacy of parathyroid hormone PTH mono-therapy and PTH anti-catabolic combination therapies on Nmp4--and wild type WT mice. The scope of the research comprises the following specific aims i and ii to determine the impact of Nmp4 on the efficacy of PTH mono- and combination therapies with various anti-catabolics in ovariectomized ovx mice iii to determine the cell type-specific contributions to the enhanced response of the Nmp4-- mouse to these osteoporosis therapies. In Year 3 we determined that loss of Nmp4 increases bone marrow osteoprogenitor number and converts osteoprogenitors into super-secretor osteoblasts by elevated ribosome biogenesis and the expansion of the ER protein processing capacity. The most significant findings during the YEAR 3 period include the following Key finding 1 Nmp4-- osteoprogenitors are differentially responsive to PTHRAL and PTHZOL. Key finding 2 The Nmp4-- mice exhibited higher levels of serum osteocalcin compared to WT mice. Key finding 3 Loss of Nmp4 did not significantly alter bone resorption. Key finding 4 Loss of Nmp4 did not significantly alter serum OPGRANKL ratios. Key finding 5 Loss of Nmp4 did not significantly alter the number of bone marrow adipocytes. Key finding 6 The Nmp4-- osteoprogenitor is a super-secretor cell. Key finding 7 The Nmp4-- osteoprogenitor over-extended ER machinery is sensitized to ZOL-induced apoptosis.
- Medicine and Medical Research