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miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARγ and GREM1

The imbalance between adipogenic and osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) plays a significant role in the pathogenesis of steroid-induced osteonecrosis of the femoral head (ONFH). Several microRNAs (miRNAs) are involved in regulating adipogenesis and osteogenesis....

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Detalles Bibliográficos
Autores principales: Gu, Chenxi, Xu, Yan, Zhang, Shanfeng, Guan, Hongya, Song, Shi, Wang, Xiuli, Wang, Yisheng, Li, Yuebai, Zhao, Guoqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133594/
https://www.ncbi.nlm.nih.gov/pubmed/27910957
http://dx.doi.org/10.1038/srep38491
Descripción
Sumario:The imbalance between adipogenic and osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) plays a significant role in the pathogenesis of steroid-induced osteonecrosis of the femoral head (ONFH). Several microRNAs (miRNAs) are involved in regulating adipogenesis and osteogenesis. In this study, we established a steroid-induced ONFH rat model to identify the potential relevant miRNAs. We identified 9 up-regulated and 28 down-regulated miRNAs in the ONFH rat model. Of these, miR-27a was down-regulated and negatively correlated with peroxisome proliferator-activated receptor gamma (PPARγ) and gremlin 1 (GREM1) expression. Further studies confirmed that PPARγ and GREM1 were direct targets of miRNA-27a. Additionally, adipogenic differentiation was enhanced by miR-27a down-regulation, whereas miRNA-27a up-regulation attenuated adipogenesis and promoted osteogenesis in steroid-induced rat BMSCs. Moreover, miRNA-27a up-regulation had a stronger effect on adipogenic and osteogenic differentiation in steroid-induced rat BMSCs than si-PPARγ and si-GREM1. In conclusion, we identified 37 differentially expressed miRNAs in the steroid-induced ONFH model, of which miR-27a was down-regulated. Our results showed that miR-27a up-regulation could inhibit adipogenesis and promote osteogenesis by directly targeting PPARγ and GREM1. Thus, miR-27a is likely a key regulator of adipogenesis in steroid-induced BMSCs and a potential therapeutic target for ONFH treatment.