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Protection of primary cilia is an effective countermeasure against the impairment of osteoblast function induced by simulated microgravity

The molecular mechanism for the microgravity‐induced decrease in bone formation remains unclear and there is a lack of effective specific preventative therapies. We recently reported that primary cilia of osteoblasts became shorter and even disappeared when the cells were exposed to random positioni...

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Autores principales: Liu, Jing, Leng, Fei‐Fan, Gao, Yu‐Hai, He, Wen‐Fang, Wang, Ju‐Fang, Xian, Cory J., Ma, Hui‐Ping, Chen, Ke‐Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806295/
https://www.ncbi.nlm.nih.gov/pubmed/36512344
http://dx.doi.org/10.1111/jcmm.17628
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author Liu, Jing
Leng, Fei‐Fan
Gao, Yu‐Hai
He, Wen‐Fang
Wang, Ju‐Fang
Xian, Cory J.
Ma, Hui‐Ping
Chen, Ke‐Ming
author_facet Liu, Jing
Leng, Fei‐Fan
Gao, Yu‐Hai
He, Wen‐Fang
Wang, Ju‐Fang
Xian, Cory J.
Ma, Hui‐Ping
Chen, Ke‐Ming
author_sort Liu, Jing
collection PubMed
description The molecular mechanism for the microgravity‐induced decrease in bone formation remains unclear and there is a lack of effective specific preventative therapies. We recently reported that primary cilia of osteoblasts became shorter and even disappeared when the cells were exposed to random positioning machine (RPM)‐simulated microgravity and that the microgravity‐induced loss of osteogenic potential of osteoblasts could be attenuated when the resorption of primary cilia was prevented by treatment with 0.1 μM cytochalasin D. In the current study, it was further found that the loss of the osteogenic capacity of rat calvarial osteoblasts (ROBs) was associated with the inhibition of the BMP‐2/Smad1/5/8 signalling pathway, of which most of the signalling proteins including BMP‐2, BMPRII, Smad1/5/8 and p‐Smad1/5/8 were found localized to primary cilia. Accompanying the resorption of primary cilia following the cells being exposed to simulated microgravity, the expression levels of these signalling proteins were reduced significantly. Furthermore, the expression of miRNA‐129‐3p, a microRNA previously reported to control cilium biogenesis, was found to be reduced quickly and changed in a similar tendency with the length of primary cilia. Moreover, overexpression of miRNA‐129‐3p in ROBs significantly attenuated microgravity‐induced inhibition of BMP‐2 signalling and loss of osteogenic differentiation and mineralization. These results indicated the important role of miRNA‐129‐3p in microgravity‐induced resorption of primary cilia of osteoblasts and the potential of replenishing the miRNA‐129‐3p as an effective countermeasure against microgravity‐induced loss of primary cilia and impairment of osteoblast function.
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spelling pubmed-98062952023-01-04 Protection of primary cilia is an effective countermeasure against the impairment of osteoblast function induced by simulated microgravity Liu, Jing Leng, Fei‐Fan Gao, Yu‐Hai He, Wen‐Fang Wang, Ju‐Fang Xian, Cory J. Ma, Hui‐Ping Chen, Ke‐Ming J Cell Mol Med Original Articles The molecular mechanism for the microgravity‐induced decrease in bone formation remains unclear and there is a lack of effective specific preventative therapies. We recently reported that primary cilia of osteoblasts became shorter and even disappeared when the cells were exposed to random positioning machine (RPM)‐simulated microgravity and that the microgravity‐induced loss of osteogenic potential of osteoblasts could be attenuated when the resorption of primary cilia was prevented by treatment with 0.1 μM cytochalasin D. In the current study, it was further found that the loss of the osteogenic capacity of rat calvarial osteoblasts (ROBs) was associated with the inhibition of the BMP‐2/Smad1/5/8 signalling pathway, of which most of the signalling proteins including BMP‐2, BMPRII, Smad1/5/8 and p‐Smad1/5/8 were found localized to primary cilia. Accompanying the resorption of primary cilia following the cells being exposed to simulated microgravity, the expression levels of these signalling proteins were reduced significantly. Furthermore, the expression of miRNA‐129‐3p, a microRNA previously reported to control cilium biogenesis, was found to be reduced quickly and changed in a similar tendency with the length of primary cilia. Moreover, overexpression of miRNA‐129‐3p in ROBs significantly attenuated microgravity‐induced inhibition of BMP‐2 signalling and loss of osteogenic differentiation and mineralization. These results indicated the important role of miRNA‐129‐3p in microgravity‐induced resorption of primary cilia of osteoblasts and the potential of replenishing the miRNA‐129‐3p as an effective countermeasure against microgravity‐induced loss of primary cilia and impairment of osteoblast function. John Wiley and Sons Inc. 2022-12-13 /pmc/articles/PMC9806295/ /pubmed/36512344 http://dx.doi.org/10.1111/jcmm.17628 Text en © 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Liu, Jing
Leng, Fei‐Fan
Gao, Yu‐Hai
He, Wen‐Fang
Wang, Ju‐Fang
Xian, Cory J.
Ma, Hui‐Ping
Chen, Ke‐Ming
Protection of primary cilia is an effective countermeasure against the impairment of osteoblast function induced by simulated microgravity
title Protection of primary cilia is an effective countermeasure against the impairment of osteoblast function induced by simulated microgravity
title_full Protection of primary cilia is an effective countermeasure against the impairment of osteoblast function induced by simulated microgravity
title_fullStr Protection of primary cilia is an effective countermeasure against the impairment of osteoblast function induced by simulated microgravity
title_full_unstemmed Protection of primary cilia is an effective countermeasure against the impairment of osteoblast function induced by simulated microgravity
title_short Protection of primary cilia is an effective countermeasure against the impairment of osteoblast function induced by simulated microgravity
title_sort protection of primary cilia is an effective countermeasure against the impairment of osteoblast function induced by simulated microgravity
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806295/
https://www.ncbi.nlm.nih.gov/pubmed/36512344
http://dx.doi.org/10.1111/jcmm.17628
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