MicroRNA‑141 inhibits the differentiation of bone marrow‑derived mesenchymal stem cells in steroid‑induced osteonecrosis via E2F3

MicroRNA-141 通过 E2F3 抑制类固醇诱发的骨坏死中骨髓间充质干细胞的分化

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作者:Fei Xue, Jian Wu, Wei Feng, Ting Hao, Yuan Liu, Wenbo Wang

Abstract

Osteonecrosis of the femoral head (ONFH) affects the life of patients. MicroRNA‑141 (miR‑141) has been found associated with proliferation of bone marrow‑derived mesenchymal stem cells (BMSCs). E2F transcription factor 3 (E2F3) has been identified as the target of miR‑141 to regulate cell proliferation. The aim of the present study was to investigate whether miR‑141 and E2F3 were involved in the osteogenic differentiation of BMSCs during ONFH. BMSCs from 4‑week‑old Sprague‑Dawley rats were transduced with miR‑141 mimic or inhibitor lentiviruses. Alkaline phosphatase staining was performed to confirm osteogenic differentiation. Reverse transcription‑quantitative PCR, luciferase reporter assays and western blot analysis were also used to examine the interaction between E2F3 and miR‑141 in BMSCs from the control and ONFH rats. The lentiviral transductions were carried out successfully. The mRNA expression levels of miR‑141 in ONFH were upregulated, while those of E2F3 were downregulated compared with the control rat. The luciferase reporter assays indicated that miR‑141 could target E2F3. miR‑141 knockdown upregulated the mRNA expression levels of E2F3. In addition, osteogenic differentiation of BMSCs was inhibited following miR‑141 overexpression, but increased following miR‑141 knockdown, as evidenced by the results of the alkaline phosphatase staining and western blot analysis. In conclusion, miR‑141 inhibits the osteogenic differentiation of BMSCs in ONFH by targeting E2F3. These two molecules may represent novel candidates to examine in order to investigate the mechanism underlying ONFH.

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