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首页> 外文期刊>Biochimica et Biophysica Acta. Gene Regulatory Mechanisms >MiR-7b directly targets DC-STAMP causing suppression of NFATc1 and c-Fos signaling during osteoclast fusion and differentiation
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MiR-7b directly targets DC-STAMP causing suppression of NFATc1 and c-Fos signaling during osteoclast fusion and differentiation

机译:miR-7b直接靶向骨壳融合期间NFATC1和C-FOS信号传导的直流标记,导致抑制NFATC1和C-FOS信号传导

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摘要

DC-STAMP is a key regulating molecule of osteoclastogenesis and osteoclast precursor (OCP) fusion. Emerging lines of evidence showed that microRNAs play crucial roles in bone metabolism and osteoclast differentiation, but no microRNA has yet been reported to be directly related to OCPs fusion. Through a microarray, we found that the expression of miR-7b in RAW264.7 cells was significantly decreased after induction with M-CSF and RANKL. The overexpression of miR-7b in RAW264.7 cells attenuated the number of TRAP-positive cells number and the formation of multinucleated cells, whereas the inhibition of miR-7b enhanced osteoclastogenesis. Through a dual luciferase reporter assay, we confirmed that miR-7b directly targets DC-STAMP. Other fusogenic molecules, such as CD47, ATP6v0d2, and OC-STAMP, were detected to be down-regulated in accordance with the inhibition of DC-STAMP. Because DC-STAMP also participates in osteoclast differentiation through the ITAM-ITIM network, multiple osteoclast-specific genes in the ITAM-ITIM network were detected to identify how DC-STAMP is involved in this process. The results showed that molecules associated with the ITAM-ITIM network, such as NFATc1 and OSCAR, which are crucial in osteoclastogenesis, were consistently altered due to DC-STAMP inhibition. These findings suggest that miR-7b inhibits osteoclastogenesis and cell-cell fusion by directly targeting DC-STAMP. In addition, the inhibition of DC-STAMP and its downstream signals changed the expression of other fusogenic genes and key regulating genes, such as Nfatc1, c-fos, Akt, Irf8, Mapk1, and Traf6. In conclusion, our findings indicate that miR-7b may be a potential therapeutic target for the treatment of osteoclast-related bone disorders.
机译:DC印章是骨酸溶胶发生和破骨细胞前体(OCP)融合的关键调节分子。新兴的证据表明,微大RNAS在骨代谢和骨壳分化中起重要作用,但尚未涉及MicroRNA与OCPS融合直接相关。通过微阵列,我们发现在M-CSF和RANKL诱导后,RAW264.7细胞中miR-7b的表达显着降低。 MiR-7b在Raw264.7细胞中的过表达抑制了捕获阳性细胞数量的数量和多核细胞的形成,而MiR-7b的抑制增强了骨质细胞发生。通过双荧光素酶报告酶测定,我们证实MIR-7B直接靶向DC印记。检测到其他致沉菌分子,例如CD47,ATP6V0D2和OC印章,按照DC印记的抑制下调。由于DC-inch还通过ITAM-ITIM网络参与了骨壳化差异,因此检测到ITAM-ITIM网络中的多个骨抑制特异性基因,以识别该过程中涉及DC戳。结果表明,与ITAM-ITIM网络相关的分子,例如NFATC1和OSCAR,其在骨髓细胞发生中至关重要,由于DC印模抑制而始终如一地改变。这些发现表明MIR-7B通过直接靶向DC印记抑制骨髓细胞发生和细胞 - 细胞融合。此外,DC-RIPP及其下游信号的抑制改变了其他致致素基因和关键调节基因的表达,例如NFATC1,C-FOS,AKT,IRF8,MAPK1和TRAF6。总之,我们的研究结果表明miR-7b可以是治疗骨细胞相关骨障碍的潜在治疗靶标。

著录项

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  • 作者单位

    Department of Biomedical Materials Science School of Biomedical Engineering Third Military;

    Department of Biomedical Materials Science School of Biomedical Engineering Third Military;

    Department of Biomedical Materials Science School of Biomedical Engineering Third Military;

    Department of Biomedical Materials Science School of Biomedical Engineering Third Military;

    Department of Biomedical Materials Science School of Biomedical Engineering Third Military;

    Department of Biomedical Materials Science School of Biomedical Engineering Third Military;

    Department of Biomedical Materials Science School of Biomedical Engineering Third Military;

    National and Regional United Engineering Laboratory of Tissue Engineering Department of;

    Department of Biomedical Materials Science School of Biomedical Engineering Third Military;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
  • 关键词

    Cell fusion; DC-STAMP; MicroRNA; Osteoclastogenesis;

    机译:细胞融合;直流戳;microRNA;骨骨细胞发生;

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