Maximizing PTH Anabolic Osteoporosis Therapy. Revision
Abstract
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 PTH+RAL and PTH+ZOL. 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 OPG/RANKL 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2016
- Accession Number
- AD1024737
Entities
People
- Joseph Bidwell