Microgravity induces inhibition of osteoblastic differentiation and mineralization through abrogating primary cilia

Abstract It is well documented that microgravity in space environment leads to bone loss in astronauts. These physiological changes have also been validated by human and animal studies and modeled in cell-based analogs. However, the underlying mechanisms are elusive. In the current study, we identif...

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Autores principales:	Wengui Shi, Yanfang Xie, Jinpeng He, Jian Zhou, Yuhai Gao, Wenjun Wei, Nan Ding, Huiping Ma, Cory J. Xian, Keming Chen, Jufang Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a0be59ecfd824f6e9e318cb14dc4d29a
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spelling	oai:doaj.org-article:a0be59ecfd824f6e9e318cb14dc4d29a2021-12-02T16:06:29ZMicrogravity induces inhibition of osteoblastic differentiation and mineralization through abrogating primary cilia10.1038/s41598-017-02049-92045-2322https://doaj.org/article/a0be59ecfd824f6e9e318cb14dc4d29a2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02049-9https://doaj.org/toc/2045-2322Abstract It is well documented that microgravity in space environment leads to bone loss in astronauts. These physiological changes have also been validated by human and animal studies and modeled in cell-based analogs. However, the underlying mechanisms are elusive. In the current study, we identified a novel phenomenon that primary cilia (key sensors and functioning organelles) of rat calvarial osteoblasts (ROBs) gradually shrank and disappeared almost completely after exposure to simulated microgravity generated by a random positioning machine (RPM). Along with the abrogation of primary cilia, the differentiation, maturation and mineralization of ROBs were inhibited. We also found that the disappearance of primary cilia was prevented by treating ROBs with cytochalasin D, but not with LiCl or dynein light chain Tctex-type 1 (Dynlt1) siRNA. The repression of the differentiation, maturation and mineralization of ROBs was effectively offset by cytochalasin D treatment in microgravity conditions. Blocking ciliogenesis using intraflagellar transport protein 88 (IFT88) siRNA knockdown inhibited the ability of cytochalasin D to counteract this reduction of osteogenesis. These results indicate that the abrogation of primary cilia may be responsible for the microgravity’s inhibition on osteogenesis. Reconstruction of primary cilia may become a potential strategy against bone loss induced by microgravity.Wengui ShiYanfang XieJinpeng HeJian ZhouYuhai GaoWenjun WeiNan DingHuiping MaCory J. XianKeming ChenJufang WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wengui Shi Yanfang Xie Jinpeng He Jian Zhou Yuhai Gao Wenjun Wei Nan Ding Huiping Ma Cory J. Xian Keming Chen Jufang Wang Microgravity induces inhibition of osteoblastic differentiation and mineralization through abrogating primary cilia
description	Abstract It is well documented that microgravity in space environment leads to bone loss in astronauts. These physiological changes have also been validated by human and animal studies and modeled in cell-based analogs. However, the underlying mechanisms are elusive. In the current study, we identified a novel phenomenon that primary cilia (key sensors and functioning organelles) of rat calvarial osteoblasts (ROBs) gradually shrank and disappeared almost completely after exposure to simulated microgravity generated by a random positioning machine (RPM). Along with the abrogation of primary cilia, the differentiation, maturation and mineralization of ROBs were inhibited. We also found that the disappearance of primary cilia was prevented by treating ROBs with cytochalasin D, but not with LiCl or dynein light chain Tctex-type 1 (Dynlt1) siRNA. The repression of the differentiation, maturation and mineralization of ROBs was effectively offset by cytochalasin D treatment in microgravity conditions. Blocking ciliogenesis using intraflagellar transport protein 88 (IFT88) siRNA knockdown inhibited the ability of cytochalasin D to counteract this reduction of osteogenesis. These results indicate that the abrogation of primary cilia may be responsible for the microgravity’s inhibition on osteogenesis. Reconstruction of primary cilia may become a potential strategy against bone loss induced by microgravity.
format	article
author	Wengui Shi Yanfang Xie Jinpeng He Jian Zhou Yuhai Gao Wenjun Wei Nan Ding Huiping Ma Cory J. Xian Keming Chen Jufang Wang
author_facet	Wengui Shi Yanfang Xie Jinpeng He Jian Zhou Yuhai Gao Wenjun Wei Nan Ding Huiping Ma Cory J. Xian Keming Chen Jufang Wang
author_sort	Wengui Shi
title	Microgravity induces inhibition of osteoblastic differentiation and mineralization through abrogating primary cilia
title_short	Microgravity induces inhibition of osteoblastic differentiation and mineralization through abrogating primary cilia
title_full	Microgravity induces inhibition of osteoblastic differentiation and mineralization through abrogating primary cilia
title_fullStr	Microgravity induces inhibition of osteoblastic differentiation and mineralization through abrogating primary cilia
title_full_unstemmed	Microgravity induces inhibition of osteoblastic differentiation and mineralization through abrogating primary cilia
title_sort	microgravity induces inhibition of osteoblastic differentiation and mineralization through abrogating primary cilia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a0be59ecfd824f6e9e318cb14dc4d29a
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Microgravity induces inhibition of osteoblastic differentiation and mineralization through abrogating primary cilia

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