Role of miR-222-3p in c-Src-Mediated Regulation of Osteoclastogenesis

dc.contributor.authorTakigawa, Shinya
dc.contributor.authorChen, Andy
dc.contributor.authorWan, Qiaoqiao
dc.contributor.authorNa, Sungsoo
dc.contributor.authorSudo, Akihiro
dc.contributor.authorYokota, Hiroki
dc.contributor.authorHamamura, Kazunori
dc.contributor.departmentBiomedical Engineering, School of Engineering and Technologyen_US
dc.date.accessioned2018-07-26T20:49:19Z
dc.date.available2018-07-26T20:49:19Z
dc.date.issued2016-02-16
dc.description.abstractMicroRNAs (miRNAs) are small non-coding RNAs that play a mostly post-transcriptional regulatory role in gene expression. Using RAW264.7 pre-osteoclast cells and genome-wide expression analysis, we identified a set of miRNAs that are involved in osteoclastogenesis. Based on in silico analysis, we specifically focused on miR-222-3p and evaluated its role in osteoclastogenesis. The results show that the inhibitor of miR-222-3p upregulated the mRNA levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and tartrate-resistant acid phosphatase (TRAP), while its mimicking agent downregulated their mRNA levels. Western blot analysis showed that its inhibitor increased the protein levels of TRAP and cathepsin K, while its mimicking agent decreased their levels. Genome-wide mRNA expression analysis in the presence and absence of receptor activator of nuclear factor κ-B ligand (RANKL) predicted c-Src as a potential regulatory target of miR-222-3p. Live cell imaging using a fluorescence resonance energy transfer (FRET) technique revealed that miR-222-3p acted as an inhibitor of c-Src activity, and a partial silencing of c-Src suppressed RANKL-induced expression of TRAP and cathepsin K, as well as the number of multi-nucleated osteoclasts and their pit formation. Collectively, the study herein demonstrates that miR-222-3p serves as an inhibitor of osteoclastogenesis and c-Src mediates its inhibition of cathepsin K and TRAP.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationTakigawa, S., Chen, A., Wan, Q., Na, S., Sudo, A., Yokota, H., & Hamamura, K. (2016). Role of miR-222-3p in c-Src-Mediated Regulation of Osteoclastogenesis. International Journal of Molecular Sciences, 17(2). https://doi.org/10.3390/ijms17020240en_US
dc.identifier.issn1422-0067en_US
dc.identifier.urihttps://hdl.handle.net/1805/16835
dc.language.isoen_USen_US
dc.publisherMDPIen_US
dc.relation.isversionof10.3390/ijms17020240en_US
dc.relation.journalInternational Journal of Molecular Sciencesen_US
dc.rightsAttribution 3.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/
dc.sourcePMCen_US
dc.subjectmicroarrayen_US
dc.subjectmiRNAen_US
dc.subjectosteoclastogenesisen_US
dc.subjectRAW264.7 cellsen_US
dc.subjectc-Srcen_US
dc.titleRole of miR-222-3p in c-Src-Mediated Regulation of Osteoclastogenesisen_US
dc.typeArticleen_US
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