title: miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARγ and GREM1.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, No. 100 Kexue Road, Zhengzhou 450001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, No. 100 Kexue Road, Zhengzhou 450001, China.
authors.forename: Shanfeng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, No. 100 Kexue Road, Zhengzhou 450001, China.
authors.forename: Hongya
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, No. 100 Kexue Road, Zhengzhou 450001, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, China.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, No. 100 Kexue Road, Zhengzhou 450001, China.
authors.forename: Yuebai
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, No. 100 Kexue Road, Zhengzhou 450001, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D016207:Cytokines; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005271:Femur Head Necrosis / Q000139:chemically induced / Q000235:genetics; D020869:Gene Expression Profiling; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics*; D047495:PPAR gamma / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013256:Steroids / Q000009:adverse effects / Q000494:pharmacology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D016207:Cytokines; C107276:Grem1 protein, rat; C000594049:MIRN27 microRNA, rat; D035683:MicroRNAs; D047495:PPAR gamma; D011506:Proteins; D034741:RNA, Small Interfering; D013256:Steroids