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Connexin 43 hemichannels protect bone loss during estrogen deficiency
Estrogen deficiency in postmenopausal women is a major cause of bone loss, resulting in osteopenia, osteoporosis, and a high risk for bone fracture. Connexin 43 (Cx43) hemichannels (HCs) in osteocytes play an important role in osteocyte viability, bone formation, and remodeling. We showed here that...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476886/ https://www.ncbi.nlm.nih.gov/pubmed/31016065 http://dx.doi.org/10.1038/s41413-019-0050-2 |
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author | Ma, Liang Hua, Rui Tian, Yi Cheng, Hongyun Fajardo, Roberto Jose Pearson, Joseph J. Guda, Teja Shropshire, Daniel Brian Gu, Sumin Jiang, Jean X. |
author_facet | Ma, Liang Hua, Rui Tian, Yi Cheng, Hongyun Fajardo, Roberto Jose Pearson, Joseph J. Guda, Teja Shropshire, Daniel Brian Gu, Sumin Jiang, Jean X. |
author_sort | Ma, Liang |
collection | PubMed |
description | Estrogen deficiency in postmenopausal women is a major cause of bone loss, resulting in osteopenia, osteoporosis, and a high risk for bone fracture. Connexin 43 (Cx43) hemichannels (HCs) in osteocytes play an important role in osteocyte viability, bone formation, and remodeling. We showed here that estrogen deficiency reduced Cx43 expression and HC function. To determine if functional HCs protect osteocytes and bone loss during estrogen deficiency, we adopted an ovariectomy model in wild-type (WT) and two transgenic Cx43 mice: R76W (dominant-negative mutant inhibiting only gap junction channels) and Cx43 Δ130–136 (dominant-negative mutant compromising both gap junction channels and HCs). The bone mineral density (BMD), bone structure, and histomorphometric changes of cortical and trabecular bones after ovariectomy were investigated. Our results showed that the Δ130–136 transgenic cohort had greatly decreased vertebral trabecular bone mass compared to WT and R76W mice, associated with a significant increase in the number of apoptotic osteocyte and empty lacunae. Moreover, osteoclast surfaces in trabecular and cortical bones were increased after ovariectomy in the R76W and WT mice, respectively, but not in ∆130–136 mice. These data demonstrate that impairment of Cx43 HCs in osteocytes accelerates vertebral trabecular bone loss and increase in osteocyte apoptosis, and further suggest that Cx43 HCs in osteocytes protect trabecular bone against catabolic effects due to estrogen deficiency. |
format | Online Article Text |
id | pubmed-6476886 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64768862019-04-23 Connexin 43 hemichannels protect bone loss during estrogen deficiency Ma, Liang Hua, Rui Tian, Yi Cheng, Hongyun Fajardo, Roberto Jose Pearson, Joseph J. Guda, Teja Shropshire, Daniel Brian Gu, Sumin Jiang, Jean X. Bone Res Article Estrogen deficiency in postmenopausal women is a major cause of bone loss, resulting in osteopenia, osteoporosis, and a high risk for bone fracture. Connexin 43 (Cx43) hemichannels (HCs) in osteocytes play an important role in osteocyte viability, bone formation, and remodeling. We showed here that estrogen deficiency reduced Cx43 expression and HC function. To determine if functional HCs protect osteocytes and bone loss during estrogen deficiency, we adopted an ovariectomy model in wild-type (WT) and two transgenic Cx43 mice: R76W (dominant-negative mutant inhibiting only gap junction channels) and Cx43 Δ130–136 (dominant-negative mutant compromising both gap junction channels and HCs). The bone mineral density (BMD), bone structure, and histomorphometric changes of cortical and trabecular bones after ovariectomy were investigated. Our results showed that the Δ130–136 transgenic cohort had greatly decreased vertebral trabecular bone mass compared to WT and R76W mice, associated with a significant increase in the number of apoptotic osteocyte and empty lacunae. Moreover, osteoclast surfaces in trabecular and cortical bones were increased after ovariectomy in the R76W and WT mice, respectively, but not in ∆130–136 mice. These data demonstrate that impairment of Cx43 HCs in osteocytes accelerates vertebral trabecular bone loss and increase in osteocyte apoptosis, and further suggest that Cx43 HCs in osteocytes protect trabecular bone against catabolic effects due to estrogen deficiency. Nature Publishing Group UK 2019-04-22 /pmc/articles/PMC6476886/ /pubmed/31016065 http://dx.doi.org/10.1038/s41413-019-0050-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ma, Liang Hua, Rui Tian, Yi Cheng, Hongyun Fajardo, Roberto Jose Pearson, Joseph J. Guda, Teja Shropshire, Daniel Brian Gu, Sumin Jiang, Jean X. Connexin 43 hemichannels protect bone loss during estrogen deficiency |
title | Connexin 43 hemichannels protect bone loss during estrogen deficiency |
title_full | Connexin 43 hemichannels protect bone loss during estrogen deficiency |
title_fullStr | Connexin 43 hemichannels protect bone loss during estrogen deficiency |
title_full_unstemmed | Connexin 43 hemichannels protect bone loss during estrogen deficiency |
title_short | Connexin 43 hemichannels protect bone loss during estrogen deficiency |
title_sort | connexin 43 hemichannels protect bone loss during estrogen deficiency |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476886/ https://www.ncbi.nlm.nih.gov/pubmed/31016065 http://dx.doi.org/10.1038/s41413-019-0050-2 |
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