Ling-Wei Mao, Qin-Yi Jiang, Nan Meng, Li Xiao, Qi Zhang, Yong-Xin Chen, Lin-Juan Liu, Lei Wang
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引用次数: 0
Abstract
The aim of this study was to explore the effect and mechanism of Sirt6 on DNA damage repair in OA chondrocytes. Cartilage tissues were collected from OA patients with knee arthroplasty and traumatic amputation patients without OA. Besides, 7-week-old male C57BL/6 mice were randomly divided into Control and OA groups; CHON-001 cells of corresponding groups were treated with 10 ng/ml interleukin (IL)-1β, respectively. Subsequently, Sirt6 or siNrf2 was over-expressed in CHON-001 cells to observe the effect of Sirt6 on DNA damage and senescence of chondrocytes by IL-1β through the nuclear factor E2-related factor 2 (Nrf2) signaling pathway. The expression level of Sirt6 in human and mouse OA cartilage tissues was significantly decreased. However, 24 h of treatment with IL-1β significantly decreased the expression of Sirt6 in chondrocytes, induced DNA damage, and promoted cellular senescence. In addition, over-expression of Sirt6 promoted DNA damage repair and inhibited cellular senescence in IL-1β-induced chondrocytes. Moreover, the overexpression of Sirt6 activated the Keap1/Nrf2/HO-1 signaling pathway in chondrocytes, while knockdown of Nrf2 expression inhibited the DNA damage repair and anti-senescence effects of Sirt6 on IL-1β-treated chondrocytes. Sirt6 may reduce DNA damage and cellular senescence in OA chondrocytes induced by IL-1β through activating the Keap1/Nrf2/HO-1 signaling pathway.
本研究旨在探讨Sirt6对OA软骨细胞DNA损伤修复的影响和机制。研究采集了膝关节置换术后 OA 患者和无 OA 的创伤性截肢患者的软骨组织。此外,将7周龄雄性C57BL/6小鼠随机分为对照组和OA组,分别用10 ng/ml白细胞介素(IL)-1β处理相应组的CHON-001细胞。随后,在CHON-001细胞中过表达Sirt6或siNrf2,观察Sirt6通过核因子E2相关因子2(Nrf2)信号通路对IL-1β对软骨细胞DNA损伤和衰老的影响。Sirt6在人和小鼠OA软骨组织中的表达水平明显下降。然而,用IL-1β处理24小时后,软骨细胞中Sirt6的表达明显降低,诱导DNA损伤,促进细胞衰老。此外,在IL-1β诱导的软骨细胞中,过表达Sirt6可促进DNA损伤修复并抑制细胞衰老。此外,Sirt6的过表达激活了软骨细胞中的Keap1/Nrf2/HO-1信号通路,而Nrf2的敲除抑制了Sirt6对IL-1β处理的软骨细胞的DNA损伤修复和抗衰老作用。Sirt6可通过激活Keap1/Nrf2/HO-1信号通路,减轻IL-1β诱导的OA软骨细胞的DNA损伤和细胞衰老。