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从衰老的FLS中衍生出的CRTAC1通过调节NRF2/SIRT3轴在骨关节炎进展中诱导状细胞线粒体功能障碍

Xiang Chen^1,2,3, Wang Gong^1,2,3, Pan Zhang^1,2,3

¹Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.

Acta pharmaceutica Sinica. B

|November 28, 2025

概括

骨关节炎 (OA) 中的细胞衰老涉及纤维细胞样同胞细胞 (FLS),分泌软骨酸性蛋白1 (CRTAC1). 这种蛋白质抑制了线粒体和线粒体功能,推动了OA的进展,并提供了潜在的治疗点.

科学领域:

生物化学生物化学
细胞生物学细胞生物学
类风湿病学类风湿病学

背景情况:

骨关节炎 (OA) 是一种普遍的关节疾病,与细胞衰老有关.
衰老的纤维细胞样同胞细胞 (FLS) 参与了软骨的退化.

研究的目的:

调查衰老的FLS衍生因素在OA中的作用.
阐明这些因素对关节炎发病的机制.

主要方法:

单细胞测序以确定衰老的FLS中的关键分泌因子.
在体外研究中,使用红细胞检查分子相互作用 (CRTAC1,NRF2,SIRT3,FOXO3a).
在基因操纵 (SIRT3删除) 和治疗干预 (AAV-SIRT3) 的OA体内小鼠模型.

主要成果:

软骨酸性蛋白1 (CRTAC1) 被确定为衰老的FLS所分泌的关键因素.
通过降低SIRT3表达的调节,CRTAC1抑制了线粒细胞衰变并诱导了线粒体功能障碍.
冠状细胞中的SIRT3缺乏会加速关节炎的进展,而SIRT3过度表达会缓解关节炎.
CRTAC1与NRF2结合,抑制SIRT3转录,而SIRT3的减少导致FOXO3a乙化和冠状细胞功能障碍.

结论:

衰老的FLS衍生的CRTAC1在通过线粒体功能障碍的OA进展中起着至关重要的作用.
该机制涉及CRTAC1-介导的SIRT3抑制和随后的冠状细胞降解.
准CRTAC1-SIRT3通路为OA提供了一个潜在的治疗策略.

关键词:

乙化乙化是一种在CRTAC1中,软骨的退化软骨的退化这就是FOXO3a.线粒体功能障碍线粒体功能障碍骨关节炎 (OA) 是一种在SIRT3中,SIRT3是最重要的.衰老的FLS已经过去了.

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