在类风湿性关节炎中,HSP90通过激活TRAF6/NFATc1信号来加剧骨损伤
Qian Wang1,2, Xiangying Kong1, Wanyi Guo1
1Institute of Chinese Materia Medica, China, Academy of Chinese Medicine Sciences , Beijing, China.
Inflammation
|October 30, 2023
概括
热冲击蛋白90 (HSP90) 通过增强骨质细胞分化来促进类风湿性关节炎 (RA) 的骨损伤. 抑制HSP90可能为治疗RA相关骨损伤提供了一个新的策略.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 细胞生物学 细胞生物学
背景情况:
- 类风湿性关节炎 (RA) 是一种致残的自身免疫性疾病,导致软骨和骨退化.
- 热冲击蛋白90 (HSP90) 涉及RA炎症,但其在骨破坏中的作用尚不清楚.
研究的目的:
- 研究HSP90在风湿性关节炎中的骨质细胞分化和骨破坏中的作用.
- 阐明涉及HSP90介导骨质结晶发生的信号通路.
主要方法:
- 在核因子-κB配体 (RANKL) 受体激活剂诱导的骨质细胞中评估了HSP90表达.
- 评估了三胺 (HSP90抑制剂) 对骨质细胞形成和分化的影响.
- 研究了HSP90对前体细胞过度表达的骨质细胞分化的影响.
- 分析了TNF受体相关因子6 (TRAF6) /激活T细胞1 (NFATc1) 信号的核因子的激活.
- 观察了HSP90在原诱导关节炎小鼠模型中的作用.
主要成果:
- 在RANKL诱导的骨质细胞中,HSP90的表达增加.
- 特里普托利德通过阻碍HSP90表达来抑制骨质细胞的形成和分化.
- 过度表达HSP90增强了骨质细胞分化.
- HSP90激活了TRAF6/NFATc1信号通路,促进了骨质细胞分化.
- 通过TRAF6/NFATc1激活,HSP90在通过原诱导的关节炎的老鼠模型中加剧了骨破坏.
结论:
- 通过激活TRAF6/NFATc1信号通路,HSP90促进骨质细胞分化,并加剧RA中的骨损伤.
- 向HSP90代表了预防类风湿性关节炎骨损伤的潜在治疗策略.
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