The occurrence and regional distribution of DR4 on herniated disc cells - A potential apoptosis pathway in lumbar intervertebral disc

Study Design. Intervertebral discs surgically obtained from 60 herniated patients and 5 normal individuals were examined to correlate the regional distribution of DR4-receptor and apoptosis. Objective. To explore the role of a tumor necrosis factor superfamily member DR4 and the TRAIL/DR4 mediated apoptosis in the human lumbar intervertebral disc. Summary of Background Data. The pathogenesis of lumbar degenerative intervertebral discs remains not completely understood. In herniated lumbar disc tissues, increased apoptosis and higher expression of Fas/Fas ligand and caspase-3 have been reported, suggesting a pivotal role of apoptotic mechanisms in intervertebral disc degeneration. However, it is not clear that apoptosis mediators such as TRAIL and Death Receptor 4 (DR4), which often represent different apoptosis signal pathways, contribute to the apoptosis process during the development of the degenerated intervertebral discs. Methods. Apoptosis was determined by poly(ADP-ribose) polymerase (PARP) p85 immunohistochemistry. Expression of DR4 was revealed by immunohistochemistry analysis. Statistical difference among groups was analyzed using one-way ANOVA with LSD post hoc multiple comparisons and the bivariate correlations. Results. Apoptotic cells were detected in the nucleus pulposus and anulus fibrosus of all samples. However, the number of apoptotic cells was significantly higher in the nucleus compared with the anulus. Further, there were significantly more apoptotic cells in the herniated discs compared with the normal discs. Within herniated discs, a remarkably higher percentage of positive staining cells were detected in the uncontained discs than the contained ones. Strong expression of DR4 was detected in all samples of degenerative herniated discs, whereas much weaker expression was sporadically identified in normal discs. In addition, the prevalence of apoptosis positively correlated with the severity of disc degeneration. Conclusion. The concomitant increase of DR4 expression in the regions of heavy apoptotic cell aggregation suggests that TRAIL/DR4-mediated pathway may play an important role in the apoptosis in herniated discs.