SDF1/CXCR4 axis plays a role in angiogenesis during the degeneration of intervertebral discs.

Abstract

Low back pain (LBP) is a ubiquitous disease affecting quality of life. The ingrowth of new blood vessels is an important pathological feature of LBP, but its underlying mechanisms are poorly understood. The present study aimed to investigate the influence and relative mechanism of stromal cell derived factor 1 (SDF1) on the angiogenesis of degenerated intervertebral discs. The expression of SDF1 in nucleus pulposus cells (NPCs) was upregulated and downregulated by virus transfection, and the NPCs were allocated to either the downregulation (Down), degeneration (D) or upregulation (Up) group according to the expression of SDF1. The different groups of NPCs or NPC conditioned media were co-cultured with vascular endothelial cells (VECs) under different conditions. A Cell Counting Kit-8 (CCK-8) assay, a Transwell migration assay and a tube formation assay were conducted to evaluate the influence on angiogenesis. The results showed that SDF1 was significantly up- and downregulated in the Up and Down groups, respectively. Each group of NPCs or their conditioned medium was co-cultured with VECs; the CCK-8, Transwell migration and tube formation assays showed that cell viability, chemotactic migration and the tube formation ability of VECs increased with the rise in SDF1. The aforementioned results were significantly different between each group. After adding the CXCR4 inhibitor, AMD3100, the viability, migration and tube formation of VECs were suppressed in the D and Up groups, and there was a significant difference compared with the prior to the addition of the inhibitor, while there was a declining tendency in the Down group and no significant difference following addition of the inhibitor. The results demonstrated that SDF1 is expressed in human NPCs, and the SDF1/CXCR4 axis can influence the viability, migration and tube formation of VECs and may play an important role in the angiogenesis of human degenerated discs.