Does Erythropoietin and Its Receptor may Play a Role in Human Intervertebral Disk Degeneration?

Abstract

Introduction Degeneration of lumbar intervertebral discs is considered to be a cause of low back pain and radiculopathy. Many studies have shown that intervertebral disk inflammation and axonal growth of afferent fibers innervating the disk degeneration have a principal role in this pathological process. Both mechanical compression and chemical factors within nucleus pulposus (NP) are associated with the occurrence of radiculopathy. NP contains various proinflammatory cytokines that play important roles in the chemical pathogenesis of NP-induced peripheral nerve injury. The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) is a key trigger in the pathogenesis of NP-induced inflammation and apoptosis and its inhibition can reduce NP degeneration. A class of MAPKs and p38 MAPK is phosphorylated by stress signals such as inflammatory cytokineso, smotic shock, and ischemia. Spinal cord and peripheral nerve injury cause the activation of p38 in dorsal root ganglion (DRG) neurons and spinal cord microglia. Furthermore, TNF-α phosphorylates p38 and activated p38 MAPK upregulates the biosynthesis of TNF- α. TNF and p38 are involved in neuronal cell apoptosis in peripheral nerve injuries. Erythropoietin (EPO) is a pleiotropic cytokine originally identified for its role in erythropoiesis. Recent studies have demonstrated that EPO and its receptor (EPO-R) are expressed in the central nervous system, where EPO exerts neuroprotective functions. Materials and Methods The aim of the present study was to investigate whether the resident EPO and EPO-R network is present and functional in the NP of intervertebral disk in different grade of degeneration. In this study, we analyzed 20 human NP obtained following microdiscectomy. The expressions of p-p38, TNF- α, EPO, and EPOR were assessed by immunohistochemical and immunoblotting analysis. Data were analyzed by unpaired Student t-test and Dunnett t-test (significance level, p < 0.05). Results In barely degenerated disk, significantly weak expression of EPO and EPO-R was observed ( p < 0.05). Accordingly, the expression of both p-p38 and TNF in the NP was significantly lower than in well-degenerated disk ( p < 0.05). In clearly degenerated disc, a marked increase of expression of EPO and EPO-R was observed ( p < 0.05) and a consensual increase of both p-p38 and TNF in the NP was observed ( p < 0.05). Conclusion These observations suggest that the local EPO and EPO-R system is markedly engaged in the degeneration of intervertebral disk by a feasible cross-talk with network of proinflammatory cytokine such as TNF- α. These data may increase our knowledge on mechanisms underlying intervertebral disk degeneration and strongly support the possible usefulness of a therapeutic approach based on exogenous EPO administration. I confirm having declared any potential conflict of interest for all authors listed on this abstract No Disclosure of Interest None declared