microRNA-375 inhibits osteogenic differentiation by targeting runt-related transcription factor 2

Du,Feiya; Wu,Huiling; Zhou,Zhiqin; Liu,Yu

doi:10.3892/etm.2015.2477

microRNA-375 inhibits osteogenic differentiation by targeting runt-related transcription factor 2

Authors:
- Feiya Du
- Huiling Wu
- Zhiqin Zhou
- Yu Liu
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Affiliations: Department of Orthopedics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Department of Breast Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: May 7, 2015 https://doi.org/10.3892/etm.2015.2477
Pages: 207-212

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Abstract

microRNAs (miRNAs) are involved in the regulation of almost all physiological and pathological processes, including osteoblast proliferation and differentiation. miR‑375 has been reported to be aberrantly expressed in various tumor types and to inhibit cell proliferation and invasion by targeting a number of key genes. However, the effects of miR‑375 on osteogenic differentiation have not been investigated. Thus, the present study aimed to elucidate the function served by miR‑375 in osteogenic differentiation. The expression levels of miR‑375 were observed to decrease in a C2C12 cell model of osteogenic differentiation. Overexpression of miR‑375 inhibited the activity of key osteoblast markers, including osteocalcin (OC), alkaline phosphatase (ALP) and collagen, type I, α 1 (COL1A1). By contrast, inhibition of miR‑375 expression resulted in an increase in the osteogenic potential, as indicated by the enhanced expression levels of OC, ALP and COL1A1. In addition, a dual‑luciferase reporter assay indicated that runt‑related transcription factor 2 (RUNX2) was a target of miR‑375. Western blot analysis revealed that the inhibition of miR‑375 led to a significant increase in the protein expression levels of RUNX2. In addition, overexpression of RUNX2 was observed to attenuate the miR‑375‑mediated suppression of osteogenic differentiation. Therefore, the results demonstrated that miR‑375 was able to inhibit osteogenic differentiation via the regulation of RUNX2 expression.

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