Abstract
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-κB 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.
Highlights
Back pain is a leading cause of disability and job-related disability[1, 2]
Previous studies suggested that ox-LDL can decrease cell viability[18], induce reactive oxygen species production[19], reduce proteoglycan synthesis[20], increase matrix metalloproteinase 3 (MMP3) production[21] and monocyte chemoattractant protein-1 (MCP-1) expression[22] in human or bovine chondrocytes through LOX1
We investigated whether ox-LDL/LOX-1 ligand-receptor system was involved in intervertebral discs (IVDs) degeneration or herniation, and the effects of ox-LDL on cell viability and MMP3 production in cultured human nucleus pulposus cell (NPC)
Summary
Back pain is a leading cause of disability and job-related disability[1, 2]. Lumbar disc herniation (LDH) is a major cause of low back pain and sciatica[3]. Though the etiology and treatment of intervertebral disc degeneration (IVDD) has been extensively investigated, the underlying pathophysiologic mechanism remains unclear[4,5,6,7]. Abnormal lipid metabolism and atherosclerosis (AS) were implicated to be critical players in the development of age-related degenerative diseases[8, 9]. As in other age-related degenerative diseases, serum lipid levels and AS were positively correlated with LDH. 3.70 disc herniation extent, the IVDD was regarded as one inflammatory-related joint disease. Previous studies suggested that ox-LDL can decrease cell viability[18], induce reactive oxygen species production[19], reduce proteoglycan synthesis[20], increase matrix metalloproteinase 3 (MMP3) production[21] and monocyte chemoattractant protein-1 (MCP-1) expression[22] in human or bovine chondrocytes through LOX1. Whether vitamin C has similar effects on NPCs remains largely unknown
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