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J Cell Mol Med. 2019 May;23(5):3302-3316. doi: 10.1111/jcmm.14220. Epub 2019 Feb 14.

miR-181c-5p mediates simulated microgravity-induced impaired osteoblast proliferation by promoting cell cycle arrested in the G2 phase.

Author information

1
Department of Orthopedics, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
2
Department of Orthopedics, Junxie Hospital, Anhui Medical University, Nanjing, China.
3
The Key Laboratory of Aerospace Medicine, Chinese Ministry of Education, Fourth Military Medical University, Xi'an, China.
4
Department of Orthopedics, Affiliated Hospital of Air Force Aviation Medicine Research Institute, Fourth Military Medical University, Beijing, China.
5
Medical Services Section, Junxie Hospital, Anhui Medical University, Nanjing, China.
6
Department of Pharmacy, Junxie Hospital, Anhui Medical University, Nanjing, China.

Abstract

Impaired osteoblast proliferation plays fundamental roles in microgravity-induced bone loss, and cell cycle imbalance may result in abnormal osteoblast proliferation. However, whether microgravity exerts an influence on the cell cycle in osteoblasts or what mechanisms may underlie such an effect remains to be fully elucidated. Herein, we confirmed that simulated microgravity inhibits osteoblast proliferation. Then, we investigated the effect of mechanical unloading on the osteoblast cell cycle and found that simulated microgravity arrested the osteoblast cell cycle in the G2 phase. In addition, our data showed that cell cycle arrest in osteoblasts from simulated microgravity was mainly because of decreased cyclin B1 expression. Furthermore, miR-181c-5p directly inhibited cyclin B1 protein translation by binding to a target site in the 3'UTR. Lastly, we demonstrated that inhibition of miR-181c-5p partially counteracted cell cycle arrest and decreased the osteoblast proliferation induced by simulated microgravity. In conclusion, our study demonstrates that simulated microgravity inhibits cell proliferation and induces cell cycle arrest in the G2 phase in primary mouse osteoblasts partially through the miR-181c-5p/cyclin B1 pathway. This work may provide a novel mechanism of microgravity-induced detrimental effects on osteoblasts and offer a new avenue to further investigate bone loss induced by mechanical unloading.

KEYWORDS:

cell cycle; cell proliferation; cyclin B1; miR-181c-5p; osteoblast; simulated microgravity

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