The Mechanism Of Action Of Ang2 Epigenetic Modification In Pressure-mediated Disc Degeneration

[Objective] To study the effect of Angiopoietin2(Ang2)epigenetic modification on pressure-mediated human intervertebral disc degeneration and its mechanism.[Methods]Take the intervertebral disc tissue of patients with scoliosis and lumbar disc herniation,and separate normal and degenerated nucleus pulposus cells.Put normal and degenerated nucleus pulposus cells under a pressure environment of 0 MPa(normal blank group and degeneration blank group),and put normal and degenerated nucleus pulposus cells under a pressure environment of 1 MPa(normal pressure group and degeneration Pressure group),24 hours later,RT-PCR and Western Blot were used to detect the transcription and translation expression levels of target genes Ang2,Tie2,Aggrecan,collagen II and SOX9 in the 4 groups of nucleus pulposus cells.The normal nucleus pulposus cells were divided into three groups: blank group,pressure group,5-azacytidine group.After 24 hours of treatment,the above indicators were measured and the activity of nucleus pulposus cells was measured by MTT method.[Results] Pressure stimulation will cause a decrease in the expression level of related target genes(Aggrecan,collagen II and SOX9)in the extracellular matrix of the nucleus pulposus,but an increase in the expression of Ang2 and Tie2;degeneration of nucleus pulposus cells is compared with normal cells,and pressure induction Compared with the general control group,the expression of Ang2 in the nucleus pulposus cells was significantly higher in the group;DNA methylation inhibitors could reduce the transcription and translation of Ang2 and Tie2 in the nucleus pulposus cells induced by stress,and the difference was statistically significant.MTT test results showed that cell viability decreased significantly under stress-stimulated environment,DNA methylation inhibitor 5 azacytidine reversed the decrease in nucleus pulposus cell viability induced by stress,and the difference was statistically significant.[Conclusion] The extracellular environment of the nucleus pulposus characterized by excessive pressure changes,leading to a change in the epigenetic modification status of the Ang2 gene,and then overexpression,which further induces the decline of the nucleus pulposus cell activity in the intervertebral disc and the degradation of its extracellular matrix.Caused the degenerative changes of the intervertebral disc.