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Sirtuin 3 (SIRT3) maintains bone homeostasis by regulating AMPK-PGC-1β axis in mice
The mitochondrial sirtuin 3 (SIRT3) is involved in suppressing the onset of multiple pathologies, including cardiovascular disease, fatty liver, age-related hearing loss, and breast cancer. But a physiological role of SIRT3 in bone metabolism is not known. Here we show that SIRT3 is a key regulatory...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772385/ https://www.ncbi.nlm.nih.gov/pubmed/26928655 http://dx.doi.org/10.1038/srep22511 |
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author | Huh, Jeong-Eun Shin, Ji Hye Jang, Eun Sun Park, So Jeong Park, Doo Ri Ko, Ryeojin Seo, Dong-Hyun Kim, Han-Sung Lee, Seoung Hoon Choi, Yongwon Kim, Hyun Seok Lee, Soo Young |
author_facet | Huh, Jeong-Eun Shin, Ji Hye Jang, Eun Sun Park, So Jeong Park, Doo Ri Ko, Ryeojin Seo, Dong-Hyun Kim, Han-Sung Lee, Seoung Hoon Choi, Yongwon Kim, Hyun Seok Lee, Soo Young |
author_sort | Huh, Jeong-Eun |
collection | PubMed |
description | The mitochondrial sirtuin 3 (SIRT3) is involved in suppressing the onset of multiple pathologies, including cardiovascular disease, fatty liver, age-related hearing loss, and breast cancer. But a physiological role of SIRT3 in bone metabolism is not known. Here we show that SIRT3 is a key regulatory molecule to maintain bone homeostasis. Mice deficient in SIRT3 exhibited severe osteopenia owing to increased numbers of osteoclasts. Osteoclast precursors from Sirt3−/− mice underwent increased osteoclastogenesis in response to receptor activator of nuclear factor-κB ligand (RANKL), an essential cytokine for osteoclast differentiation. SIRT3 expression from RANKL induction depended on the transcription coactivator PGC-1β (peroxisome proliferator-activated receptor-γ co-activator-1β) and the nuclear receptor ERRα (estrogen receptor-related receptor α), and that SIRT3 inhibited the differentiation by interfering with the RANKL-induced expression of PGC-1β. Thus an auto-regulatory feedback mechanism operates to induce its own inhibitor SIRT3 by PGC-1β. Moreover, Sirt3−/− osteoclast precursors reduced AMP-activated protein kinase (AMPK) phosphorylation through down-regulating the expression of AMPK. Our results suggest that a mitochondrial SIRT3 is an intrinsic inhibitor for RANKL-mediated osteoclastogenesis. |
format | Online Article Text |
id | pubmed-4772385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47723852016-03-07 Sirtuin 3 (SIRT3) maintains bone homeostasis by regulating AMPK-PGC-1β axis in mice Huh, Jeong-Eun Shin, Ji Hye Jang, Eun Sun Park, So Jeong Park, Doo Ri Ko, Ryeojin Seo, Dong-Hyun Kim, Han-Sung Lee, Seoung Hoon Choi, Yongwon Kim, Hyun Seok Lee, Soo Young Sci Rep Article The mitochondrial sirtuin 3 (SIRT3) is involved in suppressing the onset of multiple pathologies, including cardiovascular disease, fatty liver, age-related hearing loss, and breast cancer. But a physiological role of SIRT3 in bone metabolism is not known. Here we show that SIRT3 is a key regulatory molecule to maintain bone homeostasis. Mice deficient in SIRT3 exhibited severe osteopenia owing to increased numbers of osteoclasts. Osteoclast precursors from Sirt3−/− mice underwent increased osteoclastogenesis in response to receptor activator of nuclear factor-κB ligand (RANKL), an essential cytokine for osteoclast differentiation. SIRT3 expression from RANKL induction depended on the transcription coactivator PGC-1β (peroxisome proliferator-activated receptor-γ co-activator-1β) and the nuclear receptor ERRα (estrogen receptor-related receptor α), and that SIRT3 inhibited the differentiation by interfering with the RANKL-induced expression of PGC-1β. Thus an auto-regulatory feedback mechanism operates to induce its own inhibitor SIRT3 by PGC-1β. Moreover, Sirt3−/− osteoclast precursors reduced AMP-activated protein kinase (AMPK) phosphorylation through down-regulating the expression of AMPK. Our results suggest that a mitochondrial SIRT3 is an intrinsic inhibitor for RANKL-mediated osteoclastogenesis. Nature Publishing Group 2016-03-01 /pmc/articles/PMC4772385/ /pubmed/26928655 http://dx.doi.org/10.1038/srep22511 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Huh, Jeong-Eun Shin, Ji Hye Jang, Eun Sun Park, So Jeong Park, Doo Ri Ko, Ryeojin Seo, Dong-Hyun Kim, Han-Sung Lee, Seoung Hoon Choi, Yongwon Kim, Hyun Seok Lee, Soo Young Sirtuin 3 (SIRT3) maintains bone homeostasis by regulating AMPK-PGC-1β axis in mice |
title | Sirtuin 3 (SIRT3) maintains bone homeostasis by regulating AMPK-PGC-1β axis in mice |
title_full | Sirtuin 3 (SIRT3) maintains bone homeostasis by regulating AMPK-PGC-1β axis in mice |
title_fullStr | Sirtuin 3 (SIRT3) maintains bone homeostasis by regulating AMPK-PGC-1β axis in mice |
title_full_unstemmed | Sirtuin 3 (SIRT3) maintains bone homeostasis by regulating AMPK-PGC-1β axis in mice |
title_short | Sirtuin 3 (SIRT3) maintains bone homeostasis by regulating AMPK-PGC-1β axis in mice |
title_sort | sirtuin 3 (sirt3) maintains bone homeostasis by regulating ampk-pgc-1β axis in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772385/ https://www.ncbi.nlm.nih.gov/pubmed/26928655 http://dx.doi.org/10.1038/srep22511 |
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