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Anoctamin 1 controls bone resorption by coupling Cl(−) channel activation with RANKL-RANK signaling transduction
Osteoclast over-activation leads to bone loss and chloride homeostasis is fundamental importance for osteoclast function. The calcium-activated chloride channel Anoctamin 1 (also known as TMEM16A) is an important chloride channel involved in many physiological processes. However, its role in osteocl...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130328/ https://www.ncbi.nlm.nih.gov/pubmed/35610255 http://dx.doi.org/10.1038/s41467-022-30625-9 |
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author | Sun, Weijia Guo, Shuai Li, Yuheng Li, JianWei Liu, Caizhi Chen, Yafei Wang, Xuzhao Tan, Yingjun Tian, Hua Wang, Cheng Du, Ruikai Zhong, Guohui Shi, Sai Ma, Biao Qu, Chang Fu, Jingxuan Jin, Xiaoyan Zhao, Dingsheng Zhan, Yong Ling, Shukuan An, Hailong Li, Yingxian |
author_facet | Sun, Weijia Guo, Shuai Li, Yuheng Li, JianWei Liu, Caizhi Chen, Yafei Wang, Xuzhao Tan, Yingjun Tian, Hua Wang, Cheng Du, Ruikai Zhong, Guohui Shi, Sai Ma, Biao Qu, Chang Fu, Jingxuan Jin, Xiaoyan Zhao, Dingsheng Zhan, Yong Ling, Shukuan An, Hailong Li, Yingxian |
author_sort | Sun, Weijia |
collection | PubMed |
description | Osteoclast over-activation leads to bone loss and chloride homeostasis is fundamental importance for osteoclast function. The calcium-activated chloride channel Anoctamin 1 (also known as TMEM16A) is an important chloride channel involved in many physiological processes. However, its role in osteoclast remains unresolved. Here, we identified the existence of Anoctamin 1 in osteoclast and show that its expression positively correlates with osteoclast activity. Osteoclast-specific Anoctamin 1 knockout mice exhibit increased bone mass and decreased bone resorption. Mechanistically, Anoctamin 1 deletion increases intracellular Cl(−) concentration, decreases H(+) secretion and reduces bone resorption. Notably, Anoctamin 1 physically interacts with RANK and this interaction is dependent upon Anoctamin 1 channel activity, jointly promoting RANKL-induced downstream signaling pathways. Anoctamin 1 protein levels are substantially increased in osteoporosis patients and this closely correlates with osteoclast activity. Finally, Anoctamin 1 deletion significantly alleviates ovariectomy induced osteoporosis. These results collectively establish Anoctamin 1 as an essential regulator in osteoclast function and suggest a potential therapeutic target for osteoporosis. |
format | Online Article Text |
id | pubmed-9130328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91303282022-05-26 Anoctamin 1 controls bone resorption by coupling Cl(−) channel activation with RANKL-RANK signaling transduction Sun, Weijia Guo, Shuai Li, Yuheng Li, JianWei Liu, Caizhi Chen, Yafei Wang, Xuzhao Tan, Yingjun Tian, Hua Wang, Cheng Du, Ruikai Zhong, Guohui Shi, Sai Ma, Biao Qu, Chang Fu, Jingxuan Jin, Xiaoyan Zhao, Dingsheng Zhan, Yong Ling, Shukuan An, Hailong Li, Yingxian Nat Commun Article Osteoclast over-activation leads to bone loss and chloride homeostasis is fundamental importance for osteoclast function. The calcium-activated chloride channel Anoctamin 1 (also known as TMEM16A) is an important chloride channel involved in many physiological processes. However, its role in osteoclast remains unresolved. Here, we identified the existence of Anoctamin 1 in osteoclast and show that its expression positively correlates with osteoclast activity. Osteoclast-specific Anoctamin 1 knockout mice exhibit increased bone mass and decreased bone resorption. Mechanistically, Anoctamin 1 deletion increases intracellular Cl(−) concentration, decreases H(+) secretion and reduces bone resorption. Notably, Anoctamin 1 physically interacts with RANK and this interaction is dependent upon Anoctamin 1 channel activity, jointly promoting RANKL-induced downstream signaling pathways. Anoctamin 1 protein levels are substantially increased in osteoporosis patients and this closely correlates with osteoclast activity. Finally, Anoctamin 1 deletion significantly alleviates ovariectomy induced osteoporosis. These results collectively establish Anoctamin 1 as an essential regulator in osteoclast function and suggest a potential therapeutic target for osteoporosis. Nature Publishing Group UK 2022-05-24 /pmc/articles/PMC9130328/ /pubmed/35610255 http://dx.doi.org/10.1038/s41467-022-30625-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sun, Weijia Guo, Shuai Li, Yuheng Li, JianWei Liu, Caizhi Chen, Yafei Wang, Xuzhao Tan, Yingjun Tian, Hua Wang, Cheng Du, Ruikai Zhong, Guohui Shi, Sai Ma, Biao Qu, Chang Fu, Jingxuan Jin, Xiaoyan Zhao, Dingsheng Zhan, Yong Ling, Shukuan An, Hailong Li, Yingxian Anoctamin 1 controls bone resorption by coupling Cl(−) channel activation with RANKL-RANK signaling transduction |
title | Anoctamin 1 controls bone resorption by coupling Cl(−) channel activation with RANKL-RANK signaling transduction |
title_full | Anoctamin 1 controls bone resorption by coupling Cl(−) channel activation with RANKL-RANK signaling transduction |
title_fullStr | Anoctamin 1 controls bone resorption by coupling Cl(−) channel activation with RANKL-RANK signaling transduction |
title_full_unstemmed | Anoctamin 1 controls bone resorption by coupling Cl(−) channel activation with RANKL-RANK signaling transduction |
title_short | Anoctamin 1 controls bone resorption by coupling Cl(−) channel activation with RANKL-RANK signaling transduction |
title_sort | anoctamin 1 controls bone resorption by coupling cl(−) channel activation with rankl-rank signaling transduction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130328/ https://www.ncbi.nlm.nih.gov/pubmed/35610255 http://dx.doi.org/10.1038/s41467-022-30625-9 |
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