Dysregulated lipid metabolism and intervertebral disc degeneration: the important role of ox-LDL/LOX-1 in endplate chondrocyte senescence and calcification

作者全名："Bing, Tan; Xiang, Shanlin; Wang, Jisheng; Jie, Hao; Cao, Ruichao; Zhang, Zhiwei; Bin, Yu; Ma, Zhaoxin; Hu, Zhenming; Nian, Zhou"

作者地址："[Bing, Tan] Third Hosp Mian Yang, Sichuan Mental Hlth Ctr, Dept Spine Surg, Mianyang 621000, Peoples R China; [Bing, Tan; Xiang, Shanlin; Jie, Hao; Cao, Ruichao; Ma, Zhaoxin; Hu, Zhenming; Nian, Zhou] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Orthoped Lab, Chongqing 400000, Peoples R China; [Zhang, Zhiwei; Bin, Yu] Chongqing Med Univ, Dept Radiol, Affiliated Hosp 1, Chongqing 400000, Peoples R China; [Wang, Jisheng] Third Hosp Mian Yang, Sichuan Mental Hlth Ctr, Dept Pharm, Mianyang 621000, Peoples R China"

通信作者："Nian, Z (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Orthoped Lab, Chongqing 400000, Peoples R China."

来源：MOLECULAR MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001287659300001

JCR分区：Q1

影响因子：5.7

年份：2024

卷号：30

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Intervertebral disc degeneration; Cell senescence and calcification; Lipid metabolism disorders; Oxidized low-density lipoprotein; Lectin-like oxidized low-density lipoprotein receptor 1

摘要："BackgroundLipid metabolism disorders are associated with degeneration of multiple tissues and organs, but the mechanism of crosstalk between lipid metabolism disorder and intervertebral disc degeneration (IDD) has not been fully elucidated. In this study we aim to investigate the regulatory mechanism of abnormal signal of lipid metabolism disorder on intervertebral disc endplate chondrocyte (EPC) senescence and calcification.MethodsHuman intervertebral disc cartilage endplate tissue, cell model and rat hyperlipemia model were performed in this study. Histology and immunohistochemistry were used to human EPC tissue detection. TMT-labelled quantitative proteomics was used to detect differential proteins, and MRI, micro-CT, safranin green staining and immunofluorescence were performed to observe the morphology and degeneration of rat tail intervertebral discs. Flow cytometry, senescence-associated beta-galactosidase staining, alizarin red staining, alkaline phosphatase staining, DCFH-DA fluorescent probe, and western blot were performed to detect the expression of EPC cell senescence, senescence-associated secretory phenotype, calcification-related proteins and the activation of cell senescence-related signaling pathways.ResultsOur study found that the highly expressed oxidized low-density lipoprotein (ox-LDL) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in human degenerative EPC was associated with hyperlipidemia (HLP). TMT-labelled quantitative proteomics revealed enriched pathways such as cell cycle regulation, endochondral bone morphogenesis and inflammation. The rat model revealed that HLP could induce ox-LDL, LOX-1, senescence and calcification markers high expression in EPC. Moreover, we demonstrated that ox-LDL-induced EPCs senescence and calcification were dependent on the LOX-1 receptor, and the ROS/P38-MAPK/NF-kappa B signaling pathway was implicated in the regulation of senescence induced by ox-LDL/LOX-1 in cell model.ConclusionsSo our study revealed that ox-LDL/LOX-1-induced EPCs senescence and calcification through ROS/P38-MAPK/NF-kappa B signaling pathway, providing information on understanding the link between lipid metabolism disorders and IDD."

基金机构：National Natural Science Foundation of China

基金资助正文：Not applicable.