Possible involvement of the oxLDL/LOX-1 system in the pathogenesis and progression of human intervertebral disc degeneration or herniation

被引:27
作者
Li, Xinhua [1 ]
Wang, Xuejun [2 ]
Hu, Zhouyang [1 ]
Chen, Zhaoxiong [1 ]
Li, Haoxi [1 ]
Liu, Xiaoming [1 ]
Yong, Zhi Yao [1 ]
Wang, Shanjing [1 ]
Wei, Zhanying [3 ]
Han, Yingchao [1 ]
Tan, Jun [1 ]
Li, Cong [1 ]
He, Xiao Bo [4 ]
Sun, Guixin [5 ]
Wu, Desheng [1 ]
Li, Lijun [1 ]
机构
[1] Tongji Univ, Sch Med, Dept Spinal Surg, Shanghai East Hosp, 150 JiMo Rd, Shanghai 200120, Peoples R China
[2] Tongji Univ, Sch Med, Dept Cardiovasc Med, Shanghai East Hosp, Shanghai 200120, Peoples R China
[3] Shanghai Jiao Tong Univ, Metab Bone Dis & Genet Res Unit, Div Osteoporosis & Bone Dis, Dept Endocrinol & Metab,Affiliated Peoples Hosp 6, Shanghai, Peoples R China
[4] Tongji Univ, Sch Med, Shanghai East Hosp, Dept Med Imaging, 150 JiMo Rd, Shanghai 200120, Peoples R China
[5] Tongji Univ, Sch Med, Dept Traumatol, Shanghai East Hosp, 150 JiMo Rd, Shanghai 200120, Peoples R China
基金
美国国家科学基金会; 中国国家自然科学基金;
关键词
LOW-DENSITY-LIPOPROTEIN; LOW-BACK-PAIN; BOVINE ARTICULAR CHONDROCYTES; NUCLEUS PULPOSUS CELLS; LECTIN-LIKE; OXIDIZED LDL; RECEPTOR-1; LOX-1; EXPRESSION; ATHEROSCLEROSIS; BONE;
D O I
10.1038/s41598-017-07780-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Epidemiological studies have concluded that hyperlipidemia and atherosclerosis were related to intervertebral disc degeneration (IVDD). The presence of oxidized low density lipoprotein (ox-LDL) and the expression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) have not been explored in this tissue. In this study, we investigated the presence of ox-LDL and the expression of its receptor LOX-1 in non-degenerated, degenerated or herniated human intervertebral discs (IVDs). The expression of LOX-1 and matrix metalloproteinase 3 (MMP3) were studied after incubating nucleus pulposus cells (NPCs) with ox-LDL. The presence of ox-LDL and LOX-1 was positively related with the extent of IVDD in nucleus pulposus (NP), end-plate cartilage and outer annulus fibrous, but not with the extent of degeneration of inter annulus fibrous. Ox-LDL significantly reduced the viability of human NPCs in a dose and time-dependent manner, and increased the expression of MMP3 induced by LOX-1. Pretreatment with anti-human LOX-1 monoclonal antibody reversed these effects. Ox-LDL, principally mediated by LOX-1, enhanced MMP3 production in NPCs through the NF-kappa B signaling pathway. In conclusion, increased accumulation of ox-LDL and LOX-1 in IVDs indicates a specific role of the receptor-ligand interaction in degeneration or herniation of IVDs.
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收藏
页数:12
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