Rosuvastatin suppresses TNF-α-induced matrix catabolism,pyroptosis and senescence via the HMGB1/NF-κB signaling pathway in nucleus pulposus cells  

作　　者：Weijian Chen Zhihuai Deng Jianxiong Zhu Liang Yuan Shuangxing Li Yangyang Zhang Jiajun Wu Zhengqi Huang Tianyu Qin Wei Ye 

机构地区：[1]Department of Orthopedics,the Fifth Affiliated Hospital of Guangzhou Medical University,Guangzhou 510705,China [2]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Medical Research Center,Sun Yat-sen Memorial Hospital of Sun Yatsen University,Guangzhou 510120,China [3]Department of Spine Surgery,Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangzhou 510120,China [4]Department of Orthopedics,the Eighth Affiliated Hospital of Sun Yat-sen University,Shenzhen 518033,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第5期795-808,共14页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.81572197 and 82002776);the Natural Science Foundation of Guangdong Province(Nos.2020A1515011538 and 2020A1515010060);the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515010345);Guangzhou Municipal Health Commission:Featured Clinical Technique Project,Yat-sen Qihang Foundation of Sun Yat-sen Memorial Hospital(No.YXQH202204);the Special Project of Guangzhou Basic Research Plan Co-funded by Municipal Schools and Enterprises(No.2023A03J0817).

摘　　要：Intervertebral disc degeneration is mainly caused by irregular matrix metabolism in nucleus pulposus cells and involves inflammatory factors such as TNF-α.Rosuvastatin,which is widely used in the clinic to reduce cholesterol levels,exerts anti-inflammatory effects,but whether rosuvastatin participates in IDD remains unclear.The current study aims to investigate the regulatory effect of rosuvastatin on IDD and the potential mechanism.In vitro experiments demonstrate that rosuvastatin promotes matrix anabolism and suppresses catabolism in response to TNF-αstimulation.In addition,rosuvastatin inhibits cell pyroptosis and senescence induced by TNF-α.These results demonstrate the therapeutic effect of rosuvastatin on IDD.We further find that HMGB1,a gene closely related to cholesterol metabolism and the inflammatory response,is upregulated in response to TNF-αstimulation.HMGB1 inhibition or knockdown successfully alleviates TNF-α-induced ECM degradation,senescence and pyroptosis.Subsequently,we find that HMGB1 is regulated by rosuvastatin and that its overexpression abrogates the protective effect of rosuvastatin.We then verify that the NF-κB pathway is the underlying pathway regulated by rosuvastatin and HMGB1.In vivo experiments also reveal that rosuvastatin inhibits IDD progression by alleviating pyroptosis and senescence and downregulating HMGB1 and p65.This study might provide new insight into therapeutic strategies for IDD.

关 键 词：intervertebral disc degeneration ROSUVASTATIN high-mobility group box 1 NF-κB signaling pathway 

分 类 号：R681.5[医药卫生—骨科学]