Up-regulation in receptor for advanced glycation end-products in inflammatory circumstances in bovine coccygeal intervertebral disc specimens in vitro.

Study Design: This study investigated whether or not the receptor for advanced glycation end-products (RAGE) was up-regulated in inflammatory circumstances and consequently associated with aggrecan content in nucleus pulposus in vitro.

Objective: To investigate the activation of AGEs-RAGE complex by the irritation of IL-1beta in bovine intervertebral disc (IVD).

Summary Of Background Data: Although we have demonstrated that the accumulation of AGEs contributed to disc degeneration in human, it may be that acceleration in the AGEs-RAGE complex might be more important, mediated by expression levels of RAGE that increase in inflammatory mediators including IL-1beta in some tissues. Therefore, we investigated, in this study, the correlation if any between IL-1beta and AGEs-RAGE complex in bovine IVD.

Methods: Samples of bovine coccygeal IVDs were harvested (n = 6). The presence of AGEs and RAGE were identified by immunohistochemistry. Real-time polymerase chain reaction (PCR) was used to quantify the messenger RNA levels of aggrecan after 6 days' stimulation of AGEs. Real-time PCR and immunofluorescein cytochemistry were performed to analyze the expression of RAGE after 2 days' stimulation of IL-1beta. The aggrecan expressions were evaluated by real-time PCR after 2 days' stimulation of combination of AGEs and/or IL-1beta.

Results: Immunohistochemical analysis revealed that AGEs and RAGE were localized within the bovine IVDs. AGEs significantly decreased the aggrecan expression in bovine IVD as in human IVD. The RAGE expression was significantly increased by 2 days' stimulation of IL-1beta. The aggrecan expression was decreased by stimulated AGEs and IL-1beta together, although not decreased by stimulated AGEs or IL-1beta separately.

Conclusion: This is the first report to show the correlation between IL-1beta and AGEs-RAGE complex in IVD. Our results suggested that the increased RAGE expression in inflammatory circumstances and interaction with AGEs are risk factors in decreasing of aggrecan content in nucleus pulposus.