Polyol pathway mediates enhanced degradation of extracellular matrix via p38 MAPK activation in intervertebral disc of diabetic rats.

The aim of this study was to determine the significance of diabetes on degradation of intervertebral disc (IVD) extracellular matrix. Diabetic rats showed a significant increase in glucose and sorbitol contents in the IVD. The levels of aldose reductase, p38 and metalloproteinases, and degradation of metalloproteinase-derived aggrecan and type II collagen were increased, while tissue inhibitors of metalloproteinases levels were decreased in the IVD of diabetic rats. These changes were markedly affected by inhibition of aldose reductase or p38. Diabetes might contribute to enhanced matrix degradation in the IVD and the polyol pathway might mediate this process via p38 activation.