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CircSEC24A在白细胞介素-1β诱导的骨关节炎中的调控作用及机制

Regulatory effect and mechanism of CircSEC24A in IL-1β-induced osteoarthritis.

作者信息

Wang Yuanrui, Chen Xiaochao, Chen Yongfeng, Sun Qiang, Wang Huayi

机构信息

Department of Orthopaedics, Xijing Hospital, The Air Force Military Medical University, Xi'an, Shaanxi, China.

出版信息

Arch Physiol Biochem. 2025 Apr;131(2):188-198. doi: 10.1080/13813455.2024.2404975. Epub 2024 Sep 27.

DOI:10.1080/13813455.2024.2404975
PMID:39328069
Abstract

Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration and damage. Increasing circular RNAs (circRNAs) have been identified to participate in the pathogenesis of OA. Hsa_circ_0128006 (also known as circSEC24) was reported as an upregulated circRNA in OA tissues, but its biological role and underlying mechanism in OA are still to be discussed. circSEC24A and NAMPT expression levels were upregulated, and miR-515-5p was reduced in OA cartilage tissues and IL-1β-treated CHON-001 cells. The absence of circSEC24A overturned IL-1β-induced suppression of cell viability and promotion of oxidative stress, apoptosis, extracellular matrix (ECM) degradation, and inflammation in CHON-001 cells. Mechanistically, circSEC24A acted as a molecular sponge for miR-515-5p to affect NAMPT expression. CircSEC24A knockdown could attenuate IL-1β-triggered CHON-001 cell injury partly via the miR-515-5p/NAMPT axis, providing new insight into the underlying application of circSEC24A in OA treatment.

摘要

骨关节炎(OA)是一种以关节软骨退变和损伤为特征的慢性关节疾病。越来越多的环状RNA(circRNA)已被证实参与OA的发病机制。据报道,hsa_circ_0128006(也称为circSEC24)在OA组织中是一种上调的circRNA,但其在OA中的生物学作用和潜在机制仍有待探讨。在OA软骨组织和白细胞介素-1β(IL-1β)处理的CHON-001细胞中,circSEC24A和烟酰胺磷酸核糖转移酶(NAMPT)的表达水平上调,而miR-515-5p水平降低。circSEC24A的缺失逆转了IL-1β诱导的CHON-001细胞活力抑制以及氧化应激、细胞凋亡、细胞外基质(ECM)降解和炎症的促进作用。从机制上讲,circSEC24A作为miR-515-5p的分子海绵影响NAMPT的表达。敲低circSEC24A可部分通过miR-515-5p/NAMPT轴减轻IL-1β引发的CHON-001细胞损伤,为circSEC24A在OA治疗中的潜在应用提供了新的见解。

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