PMID- 28785062 OWN - NLM STAT- MEDLINE DCOM- 20190314 LR - 20190314 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Aug 7 TI - Possible involvement of the oxLDL/LOX-1 system in the pathogenesis and progression of human intervertebral disc degeneration or herniation. PG - 7403 LID - 10.1038/s41598-017-07780-x [doi] LID - 7403 AB - 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-kappaB 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. FAU - Li, Xinhua AU - Li X AD - Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China. FAU - Wang, Xuejun AU - Wang X AD - Department of Cardiovascular Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. FAU - Hu, Zhouyang AU - Hu Z AD - Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China. FAU - Chen, Zhaoxiong AU - Chen Z AD - Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China. FAU - Li, Haoxi AU - Li H AD - Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China. FAU - Liu, Xiaoming AU - Liu X AD - Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China. FAU - Yong, Zhi Yao AU - Yong ZY AD - Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China. FAU - Wang, Shanjing AU - Wang S AD - Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China. FAU - Wei, Zhanying AU - Wei Z AD - Metabolic Bone Disease and Genetic Research Unit, Division of Osteoporosis and Bone Disease, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Han, Yingchao AU - Han Y AD - Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China. FAU - Tan, Jun AU - Tan J AD - Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China. FAU - Li, Cong AU - Li C AD - Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China. FAU - He, Xiao Bo AU - He XB AD - Department of medical imaging, Shanghai East Hospital, Tongji University, School of Medicine, 150 JiMo Road, Shanghai, 200120, China. FAU - Sun, Guixin AU - Sun G AD - Department of Traumatology, Shanghai East Hospital, Tongji University, School of Medicine, 150 JiMo Road, Shanghai, 200120, China. sunguixing@sina.com. FAU - Wu, Desheng AU - Wu D AD - Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China. eastspinesci@163.com. FAU - Li, Lijun AU - Li L AD - Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China. liliju@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170807 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Lipoproteins, LDL) RN - 0 (OLR1 protein, human) RN - 0 (Scavenger Receptors, Class E) RN - 0 (oxidized low density lipoprotein) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Adult MH - Aged MH - Cell Survival MH - Cells, Cultured MH - Disease Progression MH - Humans MH - Intervertebral Disc Degeneration/*metabolism MH - Intervertebral Disc Displacement/*metabolism MH - Lipoproteins, LDL/*metabolism MH - Matrix Metalloproteinase 3/metabolism MH - Middle Aged MH - Nucleus Pulposus/metabolism MH - Scavenger Receptors, Class E/*metabolism MH - Signal Transduction PMC - PMC5547039 COIS- The authors declare that they have no competing interests. EDAT- 2017/08/09 06:00 MHDA- 2019/03/15 06:00 PMCR- 2017/08/07 CRDT- 2017/08/09 06:00 PHST- 2017/01/26 00:00 [received] PHST- 2017/07/04 00:00 [accepted] PHST- 2017/08/09 06:00 [entrez] PHST- 2017/08/09 06:00 [pubmed] PHST- 2019/03/15 06:00 [medline] PHST- 2017/08/07 00:00 [pmc-release] AID - 10.1038/s41598-017-07780-x [pii] AID - 7780 [pii] AID - 10.1038/s41598-017-07780-x [doi] PST - epublish SO - Sci Rep. 2017 Aug 7;7(1):7403. doi: 10.1038/s41598-017-07780-x.