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Diabetes Alters the Response to Bacteria by Enhancing Fibroblast Apoptosis

Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, Boston, Massachusetts 02118

Address all correspondence and requests for reprints to: Dr. Dana T. Graves, Boston University School of Dental Medicine, W-202D, 700 Albany Street, Boston, Massachusetts 02118. E-mail: dgraves{at}bu.edu.

Diabetics suffer from both more frequent bacterial infections and greater consequences of infection. However, bacteriainduced tissue destruction and the subsequent response in diabetics have received relatively little attention. To investigate this issue, we inoculated the scalp of control or db/db diabetic mice, with the pathogen Porphyromonas gingivalis, which causes connective tissue destruction in humans. Both bacteria-induced cytokine expression and tissue loss were similar in diabetic and control mice. However, there was a significantly higher rate of fibroblast-specific apoptosis in the diabetic group, which was measured as cells that were double positive for the terminal deoxynucleotidyltransferase-mediated deoxy-UTP nick end labeling assay and expression of vimentin. The higher rate of fibroblast apoptosis could be explained in the diabetic group by enhanced levels of activated caspase-3. Apoptosis was evident during the peak healing period and coincided with reduced numbers of fibroblasts, diminished collagen I and III expression, and significantly reduced formation of new connective tissue matrix in diabetic mice. Thus, diabetes may impair the healing response to bacteria-induced connective tissue loss by increasing the number of caspase-3-activated fibroblasts, leading to greater apoptosis and reduced numbers of fibroblastic cells.

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