Advanced Glycation End Products in Degenerative Nucleus Pulposus with Diabetes

Diabetes mellitus (DM) has been clinically proved as a risk factor of disc degeneration, and the accumulation of advanced glycation end products (AGEs) is known to be potentially involved in diabetes. The purpose of this study is to investigate the effect of AGEs in the degeneration process of diabetic nucleus pulposus (NP) in rats and humans. Diabetic NP cells from rat coccygeal discs were treated with different concentrations of AGEs (0, 50, and 100 mu g/ml) for 3 days, and mRNA expressions of MMP-2 and RAGE were measured by real-time RT-PCR. In addition, conditioned medium from NP cells was used to analyze protein expression of MMP-2 activity and ERK by gelatin zymography and Western blot. These experiments were repeated using human intervertebral disc samples. The immunohistochemical expression of AGEs was significantly increased in diabetic discs. In response to AGEs, an increase of MMP-2, RAGE, and ERK at both mRNA and protein expression levels was observed in diabetic NP cells. The findings suggest that AGEs and DM are associated with disc degeneration in both species. Hyperglycemia in diabetes enhances the accumulation of AGEs in the NP and triggers disc degeneration. (c) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:238-244, 2014.