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Primary cilia act as microgravity sensors by depolymerizing microtubules to inhibit osteoblastic differentiation and mineralization

文献类型：期刊论文

作者Shi, Wengui1,2,3; Zhang, Yanan1,2; Chen, Keming4; He, Jinpeng1,2; Feng, Xiu1,2,5; Wei, Wenjun1,2; Hua, Junrui1,2; Wang, Jufang1,2,5
刊名BONE
出版日期2020-07-01
卷号136页码:13
关键词Microgravity Osteoblasts Primary cilium Microtubule
ISSN号8756-3282
DOI10.1016/j.bone.2020.115346
通讯作者Wang, Jufang(jufangwang@impcas.ac.cn)
英文摘要Microgravity-induced bone deterioration is a major challenge in long-term spaceflights since the underlying mechanisms remain elusive. Previously, we reported that primary cilia of osteoblasts gradually disappeared in microgravity conditions, and cilia abrogation was necessary for the inhibition of osteogenesis induced by microgravity. However, the precise roles of primary cilia have not been fully elucidated. Here, we report that microgravity depolymerizes the microtubule network of rat calvarial osteoblasts (ROBs) reversibly but has no effect on the architecture of actin filaments. Preventing primary ciliogenesis by chloral hydrate or a small interfering RNA sequence (siRNA) targeting intraflagellar transport protein 88 (IFT88) effectively relieves microgravity-induced microtubule depolymerization, whereas the stabilization of microtubules using pharmacological approaches cannot prevent the disappearance of primary cilia in microgravity conditions. Furthermore, quantification of the number of microtubules emerging from the ciliary base body shows that microgravity significantly decreases the number of basal microtubules, which is dependent on the existence of primary cilia. Finally, microgravity-induced repression of the differentiation, maturation, and mineralization of ROBs is abrogated by the stabilization of cytoplasmic microtubules. Taken together, these data suggest that primary cilia-dependent depolymerization of microtubules is responsible for the inhibition of osteogenesis induced by microgravity. Our study provides a new perspective regarding the mechanism of microgravity-induced bone loss, supporting the previously established role of primary cilia as a sensor in bone metabolism.
WOS关键词MESENCHYMAL STEM-CELLS ; OSTEOGENIC DIFFERENTIATION ; CYTOSKELETON
资助项目National Natural Sciences Foundation of China[31870851] ; National Natural Sciences Foundation of China[81770879] ; Science and Technology Research Project of Gansu Province[145RTSA012] ; Science and Technology Research Project of Gansu Province[17JR5RA307] ; International Science & Technology Cooperation Program of China[2015DFR30940]
WOS研究方向Endocrinology & Metabolism
语种英语
WOS记录号WOS:000535131500008
出版者ELSEVIER SCIENCE INC
资助机构National Natural Sciences Foundation of China ; Science and Technology Research Project of Gansu Province ; International Science & Technology Cooperation Program of China
源URL[http://119.78.100.186/handle/113462/140836]  
专题中国科学院近代物理研究所
通讯作者Wang, Jufang
作者单位1.Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Lanzhou 730000, Peoples R China
2.Chinese Acad Sci, Inst Modern Phys, CAS Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Peoples R China
3.Lanzhou Univ, Cuiying Biomed Res Ctr, Hosp 2, Lanzhou 730030, Peoples R China
4.Joint Logist Support 940 Hosp CPLA, Inst Orthopaed, Lanzhou 730050, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Shi, Wengui,Zhang, Yanan,Chen, Keming,et al. Primary cilia act as microgravity sensors by depolymerizing microtubules to inhibit osteoblastic differentiation and mineralization[J]. BONE,2020,136:13.
APA Shi, Wengui.,Zhang, Yanan.,Chen, Keming.,He, Jinpeng.,Feng, Xiu.,...&Wang, Jufang.(2020).Primary cilia act as microgravity sensors by depolymerizing microtubules to inhibit osteoblastic differentiation and mineralization.BONE,136,13.
MLA Shi, Wengui,et al."Primary cilia act as microgravity sensors by depolymerizing microtubules to inhibit osteoblastic differentiation and mineralization".BONE 136(2020):13.

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来源：近代物理研究所

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