Inhibition of miR-93-5p promotes osteogenic differentiation in a rabbit model of trauma-induced osteonecrosis of the femoral head

抑制 miR-93-5p 可促进兔创伤性股骨头坏死模型中的成骨分化

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作者:Ying Zhang, Zhikun Zhuang, Qiushi Wei, Peifeng Li, Jitian Li, Yanan Fan, Leilei Zhang, Zhinan Hong, Wei He, Haibin Wang, Youwen Liu, Wuyin Li

Abstract

Trauma-induced osteonecrosis of the femoral head (TIONFH) is characterized by femoral head collapse accompanied by degenerative changes of the hip. We previously reported that miR-93-5p expression is abnormally high in patients with TIONFH, but the role of miR-93-5p in the TIONFH process remains unclear. Herein, we investigated the role of miR-93-5p in TIONFH in a rabbit model. Bone marrow mesenchymal stem cells (BMSCs) were used for both in vivo and in vitro experiments. A rabbit model of TIONFH was injected with BMSCs transfected with miR-93-5p inhibitor. In addition, both an miR-93-5p mimic and negative control were transfected into BMSCs. Expression of miR-93-5p was significantly increased in the model group compared with control samples. An miR-93-5p inhibitor induced the expression of bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase. Furthermore, expression of osteogenesis-related markers (BMP-2, secreted phosphoprotein 1, RUNX family transcription factor 2 and Osterix) was higher in the miR-93-5p inhibitor group, as revealed by quantitative PCR and western blotting. In addition, in vitro experimentation revealed that an miR-93-5p mimic decreased BMP-2 and TNF receptor superfamily member 11b expression, but increased receptor activator of nuclear factor-kappaB ligand expression. In summary, the miR-93-5p inhibitor could promote osteogenic differentiation by increasing BMP-2 expression during the development of TIONFH. Thus, miR-93-5p may have potential as a therapeutic target for TIONF treatment.

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