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

FEBS Open Bio. 2021 Aug;11(8):2152-2165. doi: 10.1002/2211-5463.13218. Epub 2021 Jul 16.

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.

Keywords: TIONFH; bone marrow stromal cells; miR-93-5p; osteogenesis.