MicroRNA-145 Mediates Steroid-Induced Necrosis of the Femoral Head by Targeting the OPG/RANK/RANKL Signaling Pathway

• Published in: PloS one Vol. 11; no. 7; p. e0159805
• Main Authors: Zhao, Ji-Jun, Wu, Zhao-Feng, Wang, Ling, Feng, De-Hong, Cheng, Li
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.07.2016; Public Library of Science (PLoS)
• Subjects: Acid phosphatase; Acid phosphatase (tartrate-resistant); Acid resistance; Animals; Biology and Life Sciences; Cell Line, Tumor; Development and progression; Disease; Enzyme-linked immunosorbent assay; Femur; Femur Head Necrosis - etiology; Femur Head Necrosis - metabolism; Gangrene; Gene expression; Genetic aspects; HEK293 Cells; Hip joint; Hospitals; Humans; Laboratory animals; Male; Medical prognosis; Medicine and Health Sciences; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Necrosis; Orthopedics; Osteonecrosis; Osteoprotegerin; Osteoprotegerin - genetics; Osteoprotegerin - metabolism; Polymerase chain reaction; Properties; RANK Ligand - genetics; RANK Ligand - metabolism; Rats; Rats, Sprague-Dawley; Receptor Activator of Nuclear Factor-kappa B - genetics; Receptor Activator of Nuclear Factor-kappa B - metabolism; Research and Analysis Methods; Ribonucleic acid; RNA; Rodents; Signal Transduction; Signaling; Steroids - toxicity; TRANCE protein; Transfection; Western blotting; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0159805

To investigate the role of microRNA-145 (miR-145) in steroid-induced necrosis of the femoral head (SINFH) by evaluating its effects on the OPG/RANK/RANKL signaling pathway. A rat model of SINFH was constructed via injection of the lentiviral vector pLV-shRNA-miR-145. Pathological observation was performed via tartrate-resistant acid phosphatase (TRAP) staining, and serum OPG levels were detected by ELISA. The mRNA expression levels of miR-145, OPG, RANK and RANKL in THP-1 cells were assessed by RT-PCR, and the protein expression levels of OPG, RANK and RANKL were assessed by western blotting. The expression of miR-145 in the lentivirus-mediated miR-145 group was significantly up-regulated compared with that in the control and normal groups (both P < 0.01). Serum OPG levels were decreased in SINFH rats compared with control and normal rats. The mRNA and protein expression levels of OPG in THP-1 cells decreased after transfection (all P < 0.05). By contrast, the mRNA and protein expression levels of RANK and RANKL in THP-1 cells increased after transfection (all P < 0.05). After transfection of 293T cells with an miR-145 overexpression vector, miR-145 expression in 293T cells increased significantly, while OPG mRNA and protein expression decreased significantly (all P < 0.05). MiR-145 plays a role in the occurrence of SINFH by targeting the OPG/RANK/RANKL signaling pathway.