Phenotypic research on senile osteoporosis caused by SIRT6 deficiency

Osteoporosis is a serious public bone metabolic disease. However, the mechanisms underlying bone loss combined with ageing, which is known as senile osteoporosis, remains unknown. Here we show the detailed phenotype of this disease caused by SIRT6 knock out (KO) in mice. To the best of our knowledge...

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Main Authors:	Zhang, De-Mao, Cui, Di-Xin, Xu, Ruo-Shi, Zhou, Ya-Chuan, Zheng, Li-Wei, Liu, Peng, Zhou, Xue-Dong
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932771/

id	pubmed-4932771
recordtype	oai_dc
spelling	pubmed-49327712016-07-14 Phenotypic research on senile osteoporosis caused by SIRT6 deficiency Zhang, De-Mao Cui, Di-Xin Xu, Ruo-Shi Zhou, Ya-Chuan Zheng, Li-Wei Liu, Peng Zhou, Xue-Dong Original Article Osteoporosis is a serious public bone metabolic disease. However, the mechanisms underlying bone loss combined with ageing, which is known as senile osteoporosis, remains unknown. Here we show the detailed phenotype of this disease caused by SIRT6 knock out (KO) in mice. To the best of our knowledge, this is the first study to reveal that SIRT6 is expressed in both bone marrow stroma cells and bone-related cells in both mouse and human models, which suggests that SIRT6 is an important regulator in bone metabolism. SIRT6-KO mice exhibit a significant decrease in body weight and remarkable dwarfism. The skeleton of the SIRT6-KO mouse is deficient in cartilage and mineralized bone tissue. Moreover, the osteocalcin concentration in blood is lower, which suggests that bone mass is markedly lost. Besides, the tartrate-resistant acid phosphatase 5b (TRAP5b) concentration is much higher, which suggests that bone resorption is overactive. Both trabecular and cortical bones exhibit severe osteopenia, and the bone mineral density is decreased. Moreover, double-labelling analysis shows that bone formation is much slower. To determine whether SIRT6 directly regulates bone metabolism, we cultured primary bone marrow stromal cells for osteogenesis and osteoclastogenesis separately to avoid indirect interference in vivo responses such as inflammation. Taken together, these results show that SIRT6 can directly regulate osteoblast proliferation and differentiation, resulting in attenuation in mineralization. Furthermore, SIRT6 can directly regulate osteoclast differentiation and results in a higher number of small osteoclasts, which may be related to overactive bone resorption. Nature Publishing Group 2016-06 2016-04-29 /pmc/articles/PMC4932771/ /pubmed/27357320 http://dx.doi.org/10.1038/ijos.2015.57 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/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhang, De-Mao Cui, Di-Xin Xu, Ruo-Shi Zhou, Ya-Chuan Zheng, Li-Wei Liu, Peng Zhou, Xue-Dong
spellingShingle	Zhang, De-Mao Cui, Di-Xin Xu, Ruo-Shi Zhou, Ya-Chuan Zheng, Li-Wei Liu, Peng Zhou, Xue-Dong Phenotypic research on senile osteoporosis caused by SIRT6 deficiency
author_facet	Zhang, De-Mao Cui, Di-Xin Xu, Ruo-Shi Zhou, Ya-Chuan Zheng, Li-Wei Liu, Peng Zhou, Xue-Dong
author_sort	Zhang, De-Mao
title	Phenotypic research on senile osteoporosis caused by SIRT6 deficiency
title_short	Phenotypic research on senile osteoporosis caused by SIRT6 deficiency
title_full	Phenotypic research on senile osteoporosis caused by SIRT6 deficiency
title_fullStr	Phenotypic research on senile osteoporosis caused by SIRT6 deficiency
title_full_unstemmed	Phenotypic research on senile osteoporosis caused by SIRT6 deficiency
title_sort	phenotypic research on senile osteoporosis caused by sirt6 deficiency
description	Osteoporosis is a serious public bone metabolic disease. However, the mechanisms underlying bone loss combined with ageing, which is known as senile osteoporosis, remains unknown. Here we show the detailed phenotype of this disease caused by SIRT6 knock out (KO) in mice. To the best of our knowledge, this is the first study to reveal that SIRT6 is expressed in both bone marrow stroma cells and bone-related cells in both mouse and human models, which suggests that SIRT6 is an important regulator in bone metabolism. SIRT6-KO mice exhibit a significant decrease in body weight and remarkable dwarfism. The skeleton of the SIRT6-KO mouse is deficient in cartilage and mineralized bone tissue. Moreover, the osteocalcin concentration in blood is lower, which suggests that bone mass is markedly lost. Besides, the tartrate-resistant acid phosphatase 5b (TRAP5b) concentration is much higher, which suggests that bone resorption is overactive. Both trabecular and cortical bones exhibit severe osteopenia, and the bone mineral density is decreased. Moreover, double-labelling analysis shows that bone formation is much slower. To determine whether SIRT6 directly regulates bone metabolism, we cultured primary bone marrow stromal cells for osteogenesis and osteoclastogenesis separately to avoid indirect interference in vivo responses such as inflammation. Taken together, these results show that SIRT6 can directly regulate osteoblast proliferation and differentiation, resulting in attenuation in mineralization. Furthermore, SIRT6 can directly regulate osteoclast differentiation and results in a higher number of small osteoclasts, which may be related to overactive bone resorption.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932771/
_version_	1613604325808930816

Phenotypic research on senile osteoporosis caused by SIRT6 deficiency

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