Effect of miR-125 a/TRAF6/NFATC1 loop mediates on osteoclastogenesis
YANG Li
ZHAO Xinlan
LEI Dandan
LIAO Bin
QIN Aiping
Abstract：Objective To investigate the effect of miR-125 a in the process of osteoclast .Methods Monocyte colony stimulating factor (M-CSF) and nuclear factor kappa B ligand /receptor activator (RANKL) induced CD1+4 PBMCs to osteo-clast.The target gene bioinformatics arithmetic predictive miR-125a and miR-125a binding to initiate transcription factor sub region .To detect the expression of miR-125 a using real-time quantitative PCR and other related genes .Overexpression experi-ments and inhibition test were used to investigate the relationship between effect of miR -125 a in osteoclast differentiation and target gene .Used the luciferase reporter gene experiments to verify the combination between miR -125 a and its target gene .Re-sults (1) miR-125a expression in CD1+4 PBMCs precursor cells showed high expression level , with a continuation of the in-duction time , the expression decreased gradually , and reached the lowest value at fifteenth days , which showed that the ex-pression of miR-125a revealed a clear downward trend in osteoclast differentiation process .(2) miR-125a are involved in the regulation of RANKL and M /CSF induced osteoclast differentiation , over expression of miR-125 a significantly inhibited the expression of mRNA and CD1+4 PBMCs TRAP and NFATc1 to differentiate into osteoclasts.(3) miR-125a direct effect on tar-get gene expression of tumor necrosis factor related factor 6 (TRAF6), TRAF6 is a transcription factor of the RANKL/RANK/NFATc1 signaling pathway, overexpression of miR-125a decreased the protein expression level of TRAF 6, but no significant change of TRAF6 mRNA level were found .Conclusion It proved that the miR-125 a played an important role in the regulation of osteoclast differentiation by acting on the new TRAF 6/NFATC1/miR-125a negative feedback control loop , expression and regulation of miR-125a may become a new therapeutic target for metabolic bone diseases .
Keywords：microRNAOsteoclastTranscription factorTarget geneNegative feedback
Publication Date：2014-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 1160-1164 )