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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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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
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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.
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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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