The Distribution Of TRAIL/DR4 On Degenerated Disc Cell: A Potential Apoptosis-induced Pathway

Study design: we detected the expression of the cleavage of the caspase substrate PARP p85 fragment and the distribution of TRAIL/DR4 in intervertebral disc tissues surgically obtained from patients who suffered from intervertebral disc herniation and healthy males by immunohistochemical method.Objectives:To make clear whether tumor necrosis factor superfamily member DR4 and TRAIL can express on herniated intervertebral disc so that we can manifested whether the apoptosis following the TRAIL/DR4 pathway existed in intervertebral disc tissue.Background: A geat number of reaserches indicate intervertebral disc degeneration involves in intervertebral disc apoptosis. The underlying mechanism of apoptosis in degenerated intervertebral disc remains unknown. So far,three different apoptosis-induced death factor have been discovered,that is, FasL,TNF-αand TRAIL, which precipitate apoptosis by death induced signal pathway. Though some study haveinvestigated the role of apoptosis mechanism, it is unknown that whether tumor necrosis factor superfamily other members-such as DR4,DR5 and its ligand can express on degenerated intervertebral disc or its conjugation can induce apoptosis in cataplasia intervertebral disc tissue.Methods: In experimental group,a total of 60 intervertebral disc tissue were surgically obtained from 60 patients who suffered from intervertebral disc herniation or lumbar stenosis;Each included annulus and nucleus. In control group,7 intervertebral disc tissue were obtained from 7 penalty persons who were strong and healthy before death. All discs were embedded in paraffin,then ,made up to slices for analysis of immunohistochemical.At last, positive cell on the different areas of the disc tissues, including nucleus and annulus,were analyzed and counted separately in five HIF(400×) and then added to make statistical analysis.Result: In experimental group, The expression of PARP , DR4 and TRAIL was found obviously in all of disc slides including annulus and nucleus.There were higher percentage of staining cells in the nucleus than in the annulus of degenerative discs. Higher percentage of positive staining cells were detected in uncontained discs than contained ones .Apoptosis are pronouncedly affected in the nucleus which is similar to the degenerative sites of disc. furthermore,apoptosis gradually increased with the progress of disc degenerated degrees.In control group, positive cells distributed sparsely on annulus and nucleus so that the expression percentages were lower relatively. So ,p-values of less than 0.05 was considered to be statistically significant between two groups.Conclusion: Tumor necrosis factor superfamily member DR4 /TRAIL distributed on herniated intervertebral disc ,so, the result suggests that the apoptosis in herniated discs follows the third death receptor pathway,that is, TRAIL/DR4-mediated pathway.