Increased Apoptosis, Expression of Matrix Degrading Enzymes and Inflammatory Cytokines of Annulus Fibrosus Cells in Genetically Engineered Diabetic Rats: Implication for Intervertebral Disc Degeneration
Objective: To investigate the effect of diabetes mellitus (DM) on apoptosis, expression of matrix degrading enzymes and inflammatory cytokines of intervertebral disc cells in genetically engineered OLETF (diabetic) and LETO (control) rats.
Methods: Lumbar disc tissues were obtained from 6-month old OLETF and LETO rats (10 each). We examined the annulus fibrosus (AF) using TUNEL, Western blotting, reverse transcription polymerase chain reaction, and histological analysis. The expression of matrix degrading enzymes, Fas (apoptosis-related protein) and inflammatory cytokines of AF cells were evaluated by semiquantitative analysis of densitometry.
Results: OLETF rats showed increased body weight and abnormal 2-hour glucose tolerance tests compared to LETO rats. The apoptosis index and the degree of expression of Fas of AF cells were statistically higher in the OLETF rats. The degree of expression of matrix metalloproteinase-1, -2, -3 and -13 and tissue inhibitor of metalloproteinase-1 and -2 was statistically higher in the OLETF rats. The expression of interleukin-1 and -6 and tumor necrosis factor-α was statistically higher in the OLETF rats. Finally, histological analysis showed more severe fibrosis and loss of lamellar pattern in AF tissues of OLETF rats.
Conclusion: Our results suggest that diabetes mellitus is associated with increased apoptosis and expression of matrix degrading enzymes and inflammatory cytokines in AF cells. This results in more severe fibrosis and loss of lamellar pattern of AF, which leads to intervertebral disc degeneration. Strict blood glucose control might be important to delay or prevent early intervertebral disc degeneration in patients with DM.