MicroRNA-34a alleviates steroid-induced avascular necrosis of femoral head by targeting Tgif2 through OPG/RANK/RANKL signaling pathway

• Published in: Experimental biology and medicine (Maywood, N.J.) N.J.), 2017-06, Vol.242 (12), p.1234-1243
• Main Authors: Peng, Wu-Xun, Ye, Chuan, Dong, Wen-Tao, Yang, Lei-Luo, Wang, Chun-Qing, Wei, Ze-An, Wu, Jian-Hua, Li, Qing, Deng, Jin, Zhang, Jian
• Format: Article
• Language: English
• Subjects: Animals; Femur Head Necrosis - chemically induced; Femur Head Necrosis - metabolism; Gene Expression Regulation - drug effects; Glucocorticoids - toxicity; Homeodomain Proteins - metabolism; Male; Methylprednisolone - toxicity; MicroRNAs - metabolism; MicroRNAs - pharmacology; Original Research; Osteoprotegerin - metabolism; RANK Ligand - metabolism; Rats; Rats, Sprague-Dawley; Receptor Activator of Nuclear Factor-kappa B - metabolism; Repressor Proteins - metabolism; Signal Transduction - drug effects
• ISSN: 1535-3702; 1535-3699; 1535-3699
• DOI: 10.1177/1535370217703975

The study aims to investigate the effect of microRNA-34a (miR-34a) targeting Tgif2 on steroid-induced avascular necrosis of femoral head (SANFH) by regulating OPG/RANK/RANKL signaling pathway. SD rats were divided into normal control and model (RNAKL rat models) groups. The model group was further assigned into model control, negative control, miR-34a mimics and miR-34a inhibitors groups. QRT-PCR was applied to detect miR-34a, Tgif2, OPG, RANK and RNAKL mRNA expressions. Femoral head tissues were collected for Micro-CT scanning and HE staining. QRT-PCR and Western blotting were used to detect expressions of miR-34a, Tgif2, OPG, RANK, RANKL and Runx2, OPN and OC in bone tissues. Dual-luciferase reporter gene assay was used to testify the target relationship between miR-34a and Tgif2. Compared with the normal control group, the model group showed increased Tgif2, RANK and RANKL mRNA expressions, but decreased miR-34a and OPG mRNA expressions. Tgif2 mRNA expression was negatively correlated with miR-34a and OPG mRNA expressions. Micro-CT showed cystic degeneration of femoral head, with decreased bone volume/total volume (BV/TV), bone surface area/bone volume and trabecular number in the model control group compared with the normal control group. Compared with the model control group, the miR-34a mimics group showed increased BV/TV and trabecular thickness and Runx2, OPN and OC expressions, while the parameters decreased in the miR-34a inhibitors group. Compared with the normal control group, the other groups showed increased Tgif2, RANK and RANKL expressions but decreased miR-34a and OPG expressions. Compared with the model control group, Tgif2, RANK and RANKL expressions decreased and miR-34a and OPG expressions increased in the miR-34a mimics group, while the miR-34a inhibitors group had a reverse trend in contrast to the miR-34a mimics group. Tgif2 is a target gene of miR-34a. In conclusion, miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway. Impact statement miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway, which can be used as a new theoretical basis for SANFH treatment.