KMID : 0578320170400030211
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Molecules and Cells 2017 Volume.40 No. 3 p.211 ~ p.221
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Transforming Growth Factor ¥â1/Smad4 Signaling Affects Osteoclast Differentiation via Regulation of miR-155 Expression
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Zhao Hong Ying
Zhang Jun Shao Hai Yu Liu Jian Wen Jin Meng Ran Chen Jin Ping Huang Ya Zeng
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Abstract
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Transforming growth factor ¥â1 (TGF¥â1)/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 differentiation of macrophage and dendritic cells. The goal of this study was to determine whether miR-155 regulates osteoclast differentiation through TGF¥â1/Smad4 signaling. Here, we present that TGF¥â1 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¥â1. The results of luciferase reporter experiments and ChIP assays demonstrated that TGF¥â1 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¥â1/Smad4 pathway. Subsequently, TRAP staining and qRT-PCR analysis revealed that silencing Smad4 impaired the TGF¥â1-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¥â1/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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KEYWORD
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miR-155, osteoclast differentiation, Smad4, TGF¥â1
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