CircGNB1通过诱导软骨细胞中的氧化应激来驱动骨关节炎的发病
Yi Liang1,2, Lifeng Shen1,2, Weiyu Ni1,2
1Department of Orthopedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Clinical and translational medicine
|August 4, 2023
概括
循环RNA GNB1 (circGNB1) 通过通过miR-152-3p/RNF219/CAV1通路促进氧化应激加剧关节炎. 准circGNB1为骨关节炎提供了一个潜在的治疗策略.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 生物化学 生物化学
背景情况:
- 循环RNAs (circRNAs) 是生物过程的关键调节者.
- 骨关节炎 (OA) 是一种与衰老和氧化应激相关的退行性关节疾病.
- circGNB1在OA病原和氧化应激中的作用仍然在很大程度上未被探索.
研究的目的:
- 研究circGNB1作为竞争性内源RNA (ceRNA) 的功能.
- 确定circGNB1在调节与年龄相关的关节炎 (OA) 中氧化应激和病理过程中的作用.
- 阐明circGNB1在OA中的作用背后的分子机制.
主要方法:
- 在OA患者的软骨和压力下的人类软骨细胞 (HCs) 中评估circGNB1表达.
- 在HC中进行了功能增益和丧失研究,以确定circGNB1的生物学作用和目标.
- 利用中介半月体 (DMM) 鼠标模型的不稳定性来评估circGNB1调节的体内效应.
主要成果:
- 在压力高的HC和老化的软骨中,circGNB1的表达升高.
- circGNB1作为miR-152-3p的海绵,抑制其与RNF219的相互作用,并稳定CAV1.
- circGNB1过度表达在体外和体内恶化了OA的进展,而淘汰减轻了OA的严重程度.
结论:
- circGNB1通过miR-152-3p/RNF219/CAV1轴驱动OA的进展和氧化应激.
- 调节circGNB1为骨关节炎治疗提供了一个有前途的治疗途径.
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