MicroRNA‑135a‑5p is involved in osteoporosis progression through regulation of osteogenic differentiation by targeting RUNX2

Shi,Xiaocong; Zhang,Zhen

doi:10.3892/etm.2019.7849

MicroRNA‑135a‑5p is involved in osteoporosis progression through regulation of osteogenic differentiation by targeting RUNX2

Authors:
- Xiaocong Shi
- Zhen Zhang
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Affiliations: Department of Endocrinology and Metabolism, Wenzhou People's Hospital, Wenzhou, Zhejiang 325000, P.R. China, Department of Rheumatology and Immunology, Ningbo First Hospital, Ningbo, Zhejiang 315010, P.R. China
Published online on: August 5, 2019 https://doi.org/10.3892/etm.2019.7849
Pages: 2393-2400
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A number of microRNAs (miRs) have been revealed to be involved in the development of osteoporosis, including postmenopausal osteoporosis. The aim of the present study was to investigate miR‑135a‑5p expression and the cellular function of miR‑135a‑5p and its underlying mechanism in postmenopausal osteoporosis. miR‑135a‑5p expression levels in the femoral neck trabecular bone tissue fragments from postmenopausal women with or without osteoporosis were detected by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The role of miR‑135a‑5p during osteogenic differentiation was examined by performing gain‑ and loss‑of‑function experiments using miR‑135a‑5p mimic or inhibitor. TargetScan bioinformatics analysis was sued to predict targets of miR‑135a‑5p, which were confirmed using luciferase reporter assays. miR‑135a‑5p expression was significantly upregulated in femoral neck trabecular bone tissue fragments from postmenopausal women with osteoporosis compared with postmenopausal women without osteoporosis. In addition, miR‑135a‑5p expression levels significantly decreased during osteogenic differentiation in the C2C12 cell model. miR‑135a‑5p overexpression decreased the osteogenic potential of C2C12 cells, as miR‑135a‑5p overexpression significantly reduced the expression levels of several key osteoblast markers, whilst miR‑135a‑5p knockdown had the opposite effect. Furthermore, the current study demonstrated that RUNX2 was a direct target of miR‑135a‑5p. Rescue experiments indicated that RUNX2 overexpression significantly reversed the effect of miR‑135a‑5p mimic on the osteogenic potential of C2C12 cells, indicating that miR‑135a‑5p mediates osteogenic differentiation via direct targeting of RUNX2. Taken together, these results suggest that miR‑135a‑5p may serve a role in osteoporosis progression by regulating osteogenic differentiation via RUNX2.

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