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MicroRNA-145 Mediates Steroid-Induced Necrosis of the Femoral Head by Targeting the OPG/RANK/RANKL Signaling Pathway
Author(s) -
Jijun Zhao,
ZhaoFeng Wu,
Ling Wang,
Dehong Feng,
Cheng Li
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0159805
Subject(s) - rankl , microrna , femoral head , steroid , signal transduction , medicine , bioinformatics , microbiology and biotechnology , biology , endocrinology , anatomy , receptor , genetics , gene , activator (genetics) , hormone
Objective 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. Methods 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. Results 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). Conclusion MiR-145 plays a role in the occurrence of SINFH by targeting the OPG/RANK/RANKL signaling pathway.

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