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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.3
- 수록면
- 211 - 221 (11page)
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초록· 키워드
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Transforming growth factor ?1 (TGF?1)/Smad4 signaling plays a pivotal role in maintenance of the dynamic balance between bone formation and resorption. The microRNA miR-155 has been reported to exert a significant role in the differ-entiation of macrophage and dendritic cells. The goal of this study was to determine whether miR-155 regulates osteoclast differentiation through TGF?1/Smad4 signaling. Here, we present that TGF?1 elevated miR-155 levels during osteoclast differentiation through the stimulation of M-CSF and RANKL. Additionally, we found that silencing Smad4 attenuated the upregulation of miR-155 induced by TGF?1. The results of luciferase reporter experiments and ChIP assays demonstrated that TGF?1 promoted the binding of Smad4 to the miR-155 promoter at a site located in 454 bp from the transcription start site in vivo, further verifying that miR-155 is a transcriptional target of the TGF?1/Smad4 pathway. Subsequently, TRAP staining and qRT-PCR analysis revealed that silencing Smad4 impaired the TGF?1-mediated inhibition on osteoclast differentiation. Finally, we found that miR-155 may target SOCS1 and MITF to suppress osteoclast differentiation. Taken together, we provide the first evidence that TGF?1/Smad4 signaling affects osteoclast differentiation by regulation of miR-155 expression and the use of miR-155 as a potential therapeutic target for osteoclast-related diseases shows great promise.
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참고문헌 (52)
참고문헌 신청
Androulidaki, A. / 2009 / The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs / Immunity 31:220~231
Anumanthan, G. / 2005 / Restoration of TGF-beta signalling reduces tumorigenicity in human lung cancer cells / Br J. Cancer 93:1157~1167
Bartel, D. P. / 2004 / MicroRNAs : genomics, biogenesis, mechanism, and function / Cell 116:281~297
Baud'huin, M. / 2007 / RANKL, RANK, osteoprotegerin: key partners of osteoimmunology and vascular diseases / Cell Mol. Life Sci 64:2334~2350
Boyle, W. J. / 2003 / Osteoclast differentiation and activation / Nature 423:337~342
Anumanthan, G. / 2005 / Restoration of TGF-beta signalling reduces tumorigenicity in human lung cancer cells / Br J. Cancer 93:1157~1167
Bartel, D. P. / 2004 / MicroRNAs : genomics, biogenesis, mechanism, and function / Cell 116:281~297
Baud'huin, M. / 2007 / RANKL, RANK, osteoprotegerin: key partners of osteoimmunology and vascular diseases / Cell Mol. Life Sci 64:2334~2350
Boyle, W. J. / 2003 / Osteoclast differentiation and activation / Nature 423:337~342
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