赛尔图因6通过调节骨质母细胞中循环AMP响应元素结合蛋白/CCN1/循环氧基酶2通路来改善关节炎
Sze-Kwan Lin1,2, Han-Wei Wang1,3, Chia-Tung Shun4
1Department of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
Journal of bone and mineral metabolism
|October 29, 2023
概括
赛尔图因6 (SIRT6) 通过抑制骨质母细胞中CREB/CCN1/COX2通路来抑制炎症性关节炎. 这项研究揭示了SIRT6.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- CCN1对关节炎的发展至关重要,并且通过骨质母细胞中缺氧的上调.
- 之前已经证明,Sirtuin 6 (SIRT6) 抑制了骨质母细胞中缺氧诱导的CCN1表达.
研究的目的:
- 研究循环AMP响应元素结合蛋白 (CREB) /CRE在SIRT6抑制CCN1.1中的作用.
- 检查CCN1对循环氧化酶 (COX) 2合成的影响.
- 评估SIRT6在原诱导关节炎 (CIA) 的大鼠模型中的治疗潜力.
主要方法:
- 在normoxia和hypoxia下的骨质细胞培养.
- 对CCN1,-CREB,COX2和激酶的西部斑分析.
- 在体外和体内SIRT6的lentiviral过度表达.
- 路西法雷斯记者测试了CCN1促销者活动.
- 对于CREB-CCN1促进体相互作用的染色体免疫沉 (ChIP).
- 在老鼠中诱导CIA以评估SIRT6治疗.
主要成果:
- SIRT6抑制了缺氧诱导的CCN1表达和CREB酸化,可能是通过抑制CaMKII.
- CRE元素 (-286 bp) 在缺氧下对CCN1表达至关重要,SIRT6减少了CREB与该元素的结合.
- 强迫CREB表达逆转了SIRT6介导的CCN1抑制.
- 在骨质母细胞中,CCN1诱导了COX2表达.
- 在CIA大鼠中,SIRT6疗法降低了骨质母细胞中的-CREB,CCN1和COX2水平.
结论:
- 在骨质母细胞中,SIRT6调节CREB/CCN1/COX2通路.
- 在炎症性关节炎和骨再吸收中SIRT6的有益作用部分由这种途径介导.
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