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MicroRNA-17-92 cluster regulates osteoblast proliferation and differentiation

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Abstract

MicroRNAs (miRNAs) have been identified to play important functions during osteoblast proliferation, differentiation, and apoptosis. The miR-17~92 cluster is highly conserved in all vertebrates. Loss-of-function of the miR-17-92 cluster results in smaller embryos and immediate postnatal death of all animals. Germline hemizygous deletions of MIR17HG are accounted for microcephaly, short stature, and digital abnormalities in a few cases of Feingold syndrome. These reports indicate that miR-17~92 may play important function in skeletal development and mature. To determine the functional roles of miR-17~92 in bone metabolism as well as osteoblast proliferation and differentiation. Murine embryonic stem cells D3 and osteoprogenitor cell line MC3T3-E1 were induced to differentiate into osteoblasts; the expression of miR-17-92 was assayed by quantitative real-time RT-PCR. The skeletal phenotypes were assayed in mice heterozygous for miR-17~92 (miR-17~92 +/Δ). To determine the possibly direct function of miR-17~92 in bone cells, osteoblasts from miR-17~92 +/Δ mice were investigated by ex vivo cell culture. miR-17, miR-92a, and miR-20a within miR-17-92 cluster were expressed at high level in bone tissue and osteoblasts. The expression of miR-17-92 was down-regulated along with osteoblast differentiation, the lowest level was found in mature osteoblasts. Compared to wildtype controls, miR-17-92 +/Δ mice showed significantly lower trabecular and cortical bone mineral density, bone volume and trabecular number at 10 weeks old. mRNA expression of Runx2 and type I collagen was significantly lower in bone from miR-17-92 +/Δ mice. Osteoblasts from miR-17-92 +/Δ mice showed lower proliferation rate, ALP activity and less calcification. Our research suggests that the miR-17-92 cluster critically regulates bone metabolism, and this regulation is mostly through its function in osteoblasts.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81072190 to Yu X, No. 81101920 to Ma J), the Science &Technology Department of Sichuan Province (2010SZ0168 to Yu X), and the Ministry of Education of the People Republic of China ([2011]1139 to Yu X).

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Authors and Affiliations

  1. Laboratory of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, People’s Republic of China

    Mingliang Zhou, Junrong Ma, Shiju Chen, Xiang Chen & Xijie Yu

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  1. Mingliang Zhou
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Correspondence to Xijie Yu.

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Mingliang Zhou and Junrong Ma have contributed equally to this work.

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Zhou, M., Ma, J., Chen, S. et al. MicroRNA-17-92 cluster regulates osteoblast proliferation and differentiation. Endocrine 45, 302–310 (2014). https://doi.org/10.1007/s12020-013-9986-y

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