Cargando…

GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation

Osteoporosis is an age-related disease that affects millions of people. Growth differentiation factor 11 (GDF11) is a secreted member of the transforming growth factor beta (TGF-β) superfamily. Deletion of Gdf11 has been shown to result in a skeletal anterior–posterior patterning disorder. Here we s...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Weiqing, Zhou, Liyan, Zhou, Chenchen, Zhang, Shiwen, Jing, Junjun, Xie, Liang, Sun, Ningyuan, Duan, Xiaobo, Jing, Wei, Liang, Xing, Zhao, Hu, Ye, Ling, Chen, Qianming, Yuan, Quan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036163/
https://www.ncbi.nlm.nih.gov/pubmed/27653144
http://dx.doi.org/10.1038/ncomms12794
_version_ 1782455509039710208
author Liu, Weiqing
Zhou, Liyan
Zhou, Chenchen
Zhang, Shiwen
Jing, Junjun
Xie, Liang
Sun, Ningyuan
Duan, Xiaobo
Jing, Wei
Liang, Xing
Zhao, Hu
Ye, Ling
Chen, Qianming
Yuan, Quan
author_facet Liu, Weiqing
Zhou, Liyan
Zhou, Chenchen
Zhang, Shiwen
Jing, Junjun
Xie, Liang
Sun, Ningyuan
Duan, Xiaobo
Jing, Wei
Liang, Xing
Zhao, Hu
Ye, Ling
Chen, Qianming
Yuan, Quan
author_sort Liu, Weiqing
collection PubMed
description Osteoporosis is an age-related disease that affects millions of people. Growth differentiation factor 11 (GDF11) is a secreted member of the transforming growth factor beta (TGF-β) superfamily. Deletion of Gdf11 has been shown to result in a skeletal anterior–posterior patterning disorder. Here we show a role for GDF11 in bone remodelling. GDF11 treatment leads to bone loss in both young and aged mice. GDF11 inhibits osteoblast differentiation and also stimulates RANKL-induced osteoclastogenesis through Smad2/3 and c-Fos-dependent induction of Nfatc1. Injection of GDF11 impairs bone regeneration in mice and blocking GDF11 function prevents oestrogen-deficiency-induced bone loss and ameliorates age-related osteoporosis. Our data demonstrate that GDF11 is a previously unrecognized regulator of bone remodelling and suggest that GDF11 is a potential target for treatment of osteoporosis.
format Online
Article
Text
id pubmed-5036163
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-50361632016-10-04 GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation Liu, Weiqing Zhou, Liyan Zhou, Chenchen Zhang, Shiwen Jing, Junjun Xie, Liang Sun, Ningyuan Duan, Xiaobo Jing, Wei Liang, Xing Zhao, Hu Ye, Ling Chen, Qianming Yuan, Quan Nat Commun Article Osteoporosis is an age-related disease that affects millions of people. Growth differentiation factor 11 (GDF11) is a secreted member of the transforming growth factor beta (TGF-β) superfamily. Deletion of Gdf11 has been shown to result in a skeletal anterior–posterior patterning disorder. Here we show a role for GDF11 in bone remodelling. GDF11 treatment leads to bone loss in both young and aged mice. GDF11 inhibits osteoblast differentiation and also stimulates RANKL-induced osteoclastogenesis through Smad2/3 and c-Fos-dependent induction of Nfatc1. Injection of GDF11 impairs bone regeneration in mice and blocking GDF11 function prevents oestrogen-deficiency-induced bone loss and ameliorates age-related osteoporosis. Our data demonstrate that GDF11 is a previously unrecognized regulator of bone remodelling and suggest that GDF11 is a potential target for treatment of osteoporosis. Nature Publishing Group 2016-09-22 /pmc/articles/PMC5036163/ /pubmed/27653144 http://dx.doi.org/10.1038/ncomms12794 Text en Copyright © 2016, The Author(s) 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
Liu, Weiqing
Zhou, Liyan
Zhou, Chenchen
Zhang, Shiwen
Jing, Junjun
Xie, Liang
Sun, Ningyuan
Duan, Xiaobo
Jing, Wei
Liang, Xing
Zhao, Hu
Ye, Ling
Chen, Qianming
Yuan, Quan
GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation
title GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation
title_full GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation
title_fullStr GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation
title_full_unstemmed GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation
title_short GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation
title_sort gdf11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036163/
https://www.ncbi.nlm.nih.gov/pubmed/27653144
http://dx.doi.org/10.1038/ncomms12794
work_keys_str_mv AT liuweiqing gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT zhouliyan gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT zhouchenchen gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT zhangshiwen gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT jingjunjun gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT xieliang gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT sunningyuan gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT duanxiaobo gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT jingwei gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT liangxing gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT zhaohu gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT yeling gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT chenqianming gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation
AT yuanquan gdf11decreasesbonemassbystimulatingosteoclastogenesisandinhibitingosteoblastdifferentiation