Open Access

miR-628-3p regulates osteoblast differentiation by targeting RUNX2: Possible role in atrophic non-union

  • Authors:
    • Hua Chen
    • Xinran Ji
    • Fei She
    • Yuan Gao
    • Peifu Tang
  • View Affiliations

  • Published online on: December 28, 2016     https://doi.org/10.3892/ijmm.2016.2839
  • Pages: 279-286
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Atrophic non-union is a serious complication of fractures. The underlying biological mechanisms involved in its pathogenesis are not yet completely understood. MicroRNAs (miRNAs or miRs) are a type of endogenous small non-coding RNA, which participate in various physiological and pathophysiological processes. In this study, differentially expressed miRNAs were screened in patients with atrophic non-union. In total, 4 miRNAs (miR‑149*, miR‑221, miR‑628-3p and miR‑654-5p) were upregulated and 7 miRNAs (let-7b*, miR‑220b, miR‑513a-3p, miR‑551a, miR‑576-5p, miR‑1236 and kshv-miR‑K12-6-5p) were downregulated at the fracture sites in patients with atrophic non-union. Among the upregulated miRNAs, miR‑628-3p and miR‑654-5p expression was found to be persistently decreased during osteoblast differentiation, indicating their possible inhibitory effect on osteogenesis. Gain-of-function experiment demonstrated that miR‑628-3p, but not miR‑654-5p, attenuated osteoblast differentiation. Further, in silico analysis revealed that runt-related transcription factor 2 (RUNX2), the master transcript factor for osteoblast differentiation, was the target of miR-628-3p, which had two binding site-condense regions in the 3' untranslated region. The exact binding site of miR-628-3p was further identified with luciferase reporter assay. In addition, the overexpression of miR‑628-3p appeared to be associated with the suppression of RUNX2 expression at both the mRNA and protein level, suggesting that miR‑628-3p inhibits osteoblast differentiation via RUNX2. On the whole, the findings of this study provide evidence of the upregulation of miR‑628-3p in patients with atrophic non-union and that miR‑628-3p may exert an inhibitory effect on osteogenesis via the suppression of its target gene, RUNX2. The study provides valuable insight into the pathogenesis of atrophic non-union and suggests new potential therapeutic targets for the treatment of this disorder.
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February-2017
Volume 39 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Chen H, Ji X, She F, Gao Y and Tang P: miR-628-3p regulates osteoblast differentiation by targeting RUNX2: Possible role in atrophic non-union. Int J Mol Med 39: 279-286, 2017
APA
Chen, H., Ji, X., She, F., Gao, Y., & Tang, P. (2017). miR-628-3p regulates osteoblast differentiation by targeting RUNX2: Possible role in atrophic non-union. International Journal of Molecular Medicine, 39, 279-286. https://doi.org/10.3892/ijmm.2016.2839
MLA
Chen, H., Ji, X., She, F., Gao, Y., Tang, P."miR-628-3p regulates osteoblast differentiation by targeting RUNX2: Possible role in atrophic non-union". International Journal of Molecular Medicine 39.2 (2017): 279-286.
Chicago
Chen, H., Ji, X., She, F., Gao, Y., Tang, P."miR-628-3p regulates osteoblast differentiation by targeting RUNX2: Possible role in atrophic non-union". International Journal of Molecular Medicine 39, no. 2 (2017): 279-286. https://doi.org/10.3892/ijmm.2016.2839