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Sex‐Specific Differences in G(s)α‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone

Teriparatide, recombinant parathyroid hormone (PTH[1‐34]), and abaloparatide, an analogue of PTH related‐peptide (PTHrP[1‐34]), are both anabolic medications for osteoporosis that target the PTH receptor PTH1R. PTH1R is a G protein–coupled receptor, and the stimulatory Gs protein is an important med...

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Detalles Bibliográficos
Autores principales: Swami, Srilatha, Johnson, Joshua, Vecchi, Lawrence A, Kim, Matthew J, Lanske, Beate, Johnson, Rachelle W, Wu, Joy Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9751656/
https://www.ncbi.nlm.nih.gov/pubmed/36530190
http://dx.doi.org/10.1002/jbm4.10695
Descripción
Sumario:Teriparatide, recombinant parathyroid hormone (PTH[1‐34]), and abaloparatide, an analogue of PTH related‐peptide (PTHrP[1‐34]), are both anabolic medications for osteoporosis that target the PTH receptor PTH1R. PTH1R is a G protein–coupled receptor, and the stimulatory Gs protein is an important mediator of the anabolic actions of PTH1R activation in bone. We have published that mice lacking the α subunit of Gs in osteoprogenitors do not increase bone mass in response to PTH(1‐34). Unexpectedly, however, PTH(1‐34) still increases osteoblast numbers and bone formation rate in male mice, suggesting that PTH1R may have both Gs‐dependent and ‐independent actions in bone. Here we examine the role of Gs signaling in the anabolic actions of abaloparatide. We find that abaloparatide increases bone formation in male mice with postnatal deletion of G(s)α in Osx‐expressing osteoprogenitors (P‐G(s)α(OsxKO) mice) but not in female P‐G(s)α(OsxKO) mice. Therefore, abaloparatide has anabolic effects on bone in male but not female mice that appear to be independent of Gs‐mediated signaling. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.