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MiR-100-5p inhibits osteogenic differentiation of human bone mesenchymal stromal cells by targeting TMEM135

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Abstract

Osteoporosis is a disorder characterized by reduced bone mass, disruption of bone microarchitecture, and a propensity to fracture. The osteogenic differentiation of human bone mesenchymal stromal cells (hBMSCs) exerts a critical effect on preventing bone loss during osteoporosis. Herein, the study recognized miR-100-5p as a deregulated miRNA during osteoporosis (upregulated) and BMSC osteogenic differentiation (downregulated). miR-100-5p was upregulated in osteoporosis patients-isolated BMSCs compared to non-osteoporosis trauma patients-isolated BMSCs. hBMSCs, overexpression inhibited hBMSC proliferation and osteogenic differentiation, whereas miR-100-5p inhibition exerted opposite effects. TMEM135 was downregulated in osteoporosis and upregulated in differentiated osteoblasts, as well as downregulated upon the overexpression of miR-100-5p. MiR-100-5p directly targeted and inhibited TMEM135. In hBMSCs, TMEM135 silencing also inhibited hBMSC osteogenic differentiation. When co-transfected to hBMSCs, antagomir-100-5p promoted, whereas TMEM135 silencing inhibited hBMSC osteogenic differentiation; TMEM135 knockdown dramatically attenuated the effects of miR-100-5p inhibition. Taken together, miR-100-5p forms a regulatory axis with TMEM135 by direct binding. The miR-100-5p/TMEM135 axis modulates hBMSC differentiation into osteoblast. Considering the critical effect of BMSC osteogenesis on osteoporosis, this axis might play a role in osteoporosis, and further in vivo and clinical investigations are required.

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Acknowledgements

This study was supported by Special Precision Medicine Project of the National Key R&D Program from the Science and Technology Ministry of China (2016YFC0901203) and the Cultivate project 2021 for National Natural Science Foundation of China, Affiliated Hospital of Guizhou Medical University (gyfynsfc-2021-41). The research procedures were approved by the Ethics Committee of the Affiliated Hospital of Guiyang Medical University [2014(87)]. All enrolled patients signed the informed consent.

Funding

Special Precision Medicine Project of the National Key R&D Program from the Science and Technology Ministry China (2016YFC0901203) and the Cultivate project 2021 for National Natural Science Foundation of China, Affiliated Hospital of Guizhou Medical University (gyfynsfc-2021-41).

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Authors and Affiliations

  1. Department of Endocrinology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China

    Rui Wang, Miao Zhang, Ying Hu, Juan He, Qiao Lin & Nianchun Peng

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  1. Rui Wang
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  2. Miao Zhang
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  3. Ying Hu
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Correspondence to Nianchun Peng.

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Wang, R., Zhang, M., Hu, Y. et al. MiR-100-5p inhibits osteogenic differentiation of human bone mesenchymal stromal cells by targeting TMEM135. Human Cell 35, 1671–1683 (2022). https://doi.org/10.1007/s13577-022-00764-8

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