...
  • 主题
高级搜索  >
历史搜索 清空历史
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
【24h】

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DC-STAMP，从而在破骨细胞融合和分化过程中抑制NFATc1和c-Fos信号传导

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

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-STAMP是破骨细胞生成和破骨细胞前体（OCP）融合的关键调节分子。越来越多的证据表明，microRNA在骨代谢和破骨细胞分化中起着至关重要的作用，但尚未有任何microRNA与OCP融合直接相关的报道。通过微阵列，我们发现在用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细胞中的过表达减弱了TRAP阳性细胞的数量和多核细胞的形成，而对miR-7b的抑制则增强了破骨细胞的生成。通过双重荧光素酶报告基因测定，我们证实miR-7b直接靶向DC-STAMP。检测到其他融合分子，例如CD47，ATP6v0d2和OC-STAMP，根据对DC-STAMP的抑制而被下调。由于DC-STAMP还通过ITAM-ITIM网络参与破骨细胞分化，因此检测到了ITAM-ITIM网络中的多个破骨细胞特异性基因，以确定DC-STAMP如何参与该过程。结果表明，与ITAM-ITIM网络相关的分子，例如在破骨细胞形成中至关重要的NFATc1和OSCAR，由于受到DC-STAMP抑制而不断发生变化。这些发现表明，miR-7b通过直接靶向DC-STAMP抑制破骨细胞生成和细胞融合。此外，DC-STAMP及其下游信号的抑制改变了其他融合基因和关键调控基因的表达，例如Nfatc1，c-fos，Akt，Irf8，Mapk1和Traf6。总之，我们的发现表明，miR-7b可能是破骨细胞相关性骨疾病的潜在治疗靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号