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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2022
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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 |
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author | Swami, Srilatha Johnson, Joshua Vecchi, Lawrence A Kim, Matthew J Lanske, Beate Johnson, Rachelle W Wu, Joy Y |
author_facet | Swami, Srilatha Johnson, Joshua Vecchi, Lawrence A Kim, Matthew J Lanske, Beate Johnson, Rachelle W Wu, Joy Y |
author_sort | Swami, Srilatha |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9751656 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97516562022-12-15 Sex‐Specific Differences in G(s)α‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone Swami, Srilatha Johnson, Joshua Vecchi, Lawrence A Kim, Matthew J Lanske, Beate Johnson, Rachelle W Wu, Joy Y JBMR Plus Research Articles 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. John Wiley & Sons, Inc. 2022-11-24 /pmc/articles/PMC9751656/ /pubmed/36530190 http://dx.doi.org/10.1002/jbm4.10695 Text en © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Swami, Srilatha Johnson, Joshua Vecchi, Lawrence A Kim, Matthew J Lanske, Beate Johnson, Rachelle W Wu, Joy Y Sex‐Specific Differences in G(s)α‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone |
title | Sex‐Specific Differences in G(s)α‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone |
title_full | Sex‐Specific Differences in G(s)α‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone |
title_fullStr | Sex‐Specific Differences in G(s)α‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone |
title_full_unstemmed | Sex‐Specific Differences in G(s)α‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone |
title_short | Sex‐Specific Differences in G(s)α‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone |
title_sort | sex‐specific differences in g(s)α‐mediated signaling downstream of pth1r activation by abaloparatide in bone |
topic | Research Articles |
url | 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 |
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