| First Author | Liu R | Year | 2006 |
| Journal | Am J Pathol | Volume | 168 |
| Issue | 3 | Pages | 757-64 |
| PubMed ID | 16507891 | Mgi Jnum | J:106478 |
| Mgi Id | MGI:3618645 | Doi | 10.2353/ajpath.2006.050907 |
| Citation | Liu R, et al. (2006) Tumor necrosis factor-alpha mediates diabetes-enhanced apoptosis of matrix-producing cells and impairs diabetic healing. Am J Pathol 168(3):757-64 |
| abstractText | Diabetics suffer increased infection followed by increased apoptosis of fibroblasts and bone-lining cells during the healing process. To investigate a potential mechanism, we inoculated Porphyromonas gingivalis into the scalp of type 2 diabetic (db/db) or control mice and inhibited tumor necrosis factor alpha (TNF-alpha) with etanercept. Mice were euthanized at the early phase of infection (21 hours) or during the peak repair of the bacteria-induced wound (8 days). At 21 hours, TNF-alpha inhibition significantly reduced fibroblast apoptosis and caspase-3 activity in both diabetic and normoglycemic mice (P < 0.05). During healing etanercept reduced fibroblast apoptosis and caspase-3 activity by almost 50% in diabetic but not normoglycemic mice (P < 0.05). Concomitantly, etanercept significantly increased fibroblast number by 31% and new matrix formation by 72% in diabetic mice. When bone was examined during healing, administration of the TNF-alpha blocker reduced apoptosis of bone-lining cells by 53%, increased their number by 48%, and enhanced new bone formation by 140% in the diabetic group (P < 0.05). The degree of connective tissue and osseous healing stimulated in the diabetic mice by anti-TNF-alpha treatment was within the range that is physiologically relevant. This enhanced healing may in part be explained by block-ing TNF-alpha-induced apoptosis of critical matrix-producing cells. |
