DUSP4调控NF-κB p65及NFATc1表达抑制破骨细胞分化研究
DUSP4-mediated suppression of osteoclast differentiation through regulation of NF-κB p65 and NFATc1 expression
  
DOI:10.3969/j.issn.1006-7108.2026.05.008
中文关键词:  DUSP4  破骨细胞  NF-κB p65  NFATc1
英文关键词:DUSP4  osteoclast  NF-κB p65  NFATc1
基金项目:石河子大学第一附属医院科技计划项目(QN202131);兵团财政科技计划资助(2023CB008-34);石河子大学科研项目(ZZZC2023050);“天山英才”医药卫生高层次人才培养计划
作者单位
于洪涛 刘梦想 李柯 陈磊* 石河子大学第一附属医院,新疆 石河子 832008 
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中文摘要:
      目的 研究 DUSP4 基因对破骨细胞分化的影响,并研究其是否通过调控NF-κB p65及NFATc1来调控破骨细胞。方法 实验分为空白对照组、DUSP4过表达组、DUSP4抑制组和DUSP4空载组。通过CCK8法评估细胞活性;TRAP染色观察破骨细胞分化形态及细胞数目;运用Western blot和qPCR检测NF-κB p65、NFATc1、TRAP蛋白及基因表达水平。结果 过表达DUSP4抑制破骨细胞分化(P<0.05),且TRAP阳性细胞减少、形态呈未成熟特征;而DUSP4抑制组细胞活性增强,破骨细胞分化明显(P<0.05);Western blot和qPCR结果表明,DUSP4过表达会抑制NF-κB p65、NFATc1、TRAP蛋白和基因的表达(P<0.05),而抑制结果则相反。结论 DUSP4通过调控NF-κB p65、NFATc1,影响TRAP表达,进而抑制破骨细胞分化。
英文摘要:
      Objective To investigate the effects of DUSP4 gene on osteoclast differentiation and explore its potential regulatory mechanism through NF-κB p65 and NFATc1 signaling pathways. Methods The experimental groups included a blank control group, DUSP4 overexpression group, DUSP4 inhibition group, and DUSP4 empty vector group. Cell viability was assessed using CCK-8 assay. TRAP staining was employed to observe osteoclast differentiation morphology and quantify cell numbers. Western blotting and qPCR were performed to detect protein and gene expression levels of NF-κB p65, NFATc1, and TRAP. Results DUSP4 overexpression significantly inhibited osteoclast differentiation (P<0.05), characterized by reduced TRAP-positive cells and immature morphological features. Conversely, DUSP4 inhibition enhanced cellular activity and promoted osteoclast differentiation (P<0.05). Molecular analyses revealed that DUSP4 overexpression downregulated the protein and mRNA expression of NF-κB p65, NFATc1, and TRAP (P<0.05), while DUSP4 inhibition produced opposite effects. Conclusion DUSP4 suppresses osteoclast differentiation by modulating NF-κB p65 and NFATc1 signaling pathways, subsequently influencing TRAP expression.
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