Sex‐Specific Differences in Gsα‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone
ABSTRACT 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 impo...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-12-01
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| Series: | JBMR Plus |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jbm4.10695 |
| _version_ | 1811177758402805760 |
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| author | Srilatha Swami Joshua Johnson Lawrence A Vecchi Matthew J Kim Beate Lanske Rachelle W Johnson Joy Y Wu |
| author_facet | Srilatha Swami Joshua Johnson Lawrence A Vecchi Matthew J Kim Beate Lanske Rachelle W Johnson Joy Y Wu |
| author_sort | Srilatha Swami |
| collection | DOAJ |
| description | ABSTRACT 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 Gsα in Osx‐expressing osteoprogenitors (P‐GsαOsxKO mice) but not in female P‐GsαOsxKO 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. |
| first_indexed | 2024-04-11T06:06:34Z |
| format | Article |
| id | doaj.art-962b5a7ca153486f892fb3b1483c1987 |
| institution | Directory Open Access Journal |
| issn | 2473-4039 |
| language | English |
| last_indexed | 2024-04-11T06:06:34Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | JBMR Plus |
| spelling | doaj.art-962b5a7ca153486f892fb3b1483c19872022-12-22T04:41:28ZengWileyJBMR Plus2473-40392022-12-01612n/an/a10.1002/jbm4.10695Sex‐Specific Differences in Gsα‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in BoneSrilatha Swami0Joshua Johnson1Lawrence A Vecchi2Matthew J Kim3Beate Lanske4Rachelle W Johnson5Joy Y Wu6Division of Endocrinology, Department of Medicine Stanford University School of Medicine Stanford CA USADepartment of Medicine, Division of Clinical Pharmacology Vanderbilt University Medical Center Nashville TN USADepartment of Medicine, Division of Clinical Pharmacology Vanderbilt University Medical Center Nashville TN USADivision of Endocrinology, Department of Medicine Stanford University School of Medicine Stanford CA USARadius Health Boston MA USADepartment of Medicine, Division of Clinical Pharmacology Vanderbilt University Medical Center Nashville TN USADivision of Endocrinology, Department of Medicine Stanford University School of Medicine Stanford CA USAABSTRACT 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 Gsα in Osx‐expressing osteoprogenitors (P‐GsαOsxKO mice) but not in female P‐GsαOsxKO 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.https://doi.org/10.1002/jbm4.10695ANABOLICSGENETIC ANIMAL MODELSOSTEOBLASTSOSTEOPOROSISPTH/VIT D/FGF23 |
| spellingShingle | Srilatha Swami Joshua Johnson Lawrence A Vecchi Matthew J Kim Beate Lanske Rachelle W Johnson Joy Y Wu Sex‐Specific Differences in Gsα‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone JBMR Plus ANABOLICS GENETIC ANIMAL MODELS OSTEOBLASTS OSTEOPOROSIS PTH/VIT D/FGF23 |
| title | Sex‐Specific Differences in Gsα‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone |
| title_full | Sex‐Specific Differences in Gsα‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone |
| title_fullStr | Sex‐Specific Differences in Gsα‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone |
| title_full_unstemmed | Sex‐Specific Differences in Gsα‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone |
| title_short | Sex‐Specific Differences in Gsα‐Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone |
| title_sort | sex specific differences in gsα mediated signaling downstream of pth1r activation by abaloparatide in bone |
| topic | ANABOLICS GENETIC ANIMAL MODELS OSTEOBLASTS OSTEOPOROSIS PTH/VIT D/FGF23 |
| url | https://doi.org/10.1002/jbm4.10695 |
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