To study the role of TNF inhibitor in altering apoptosis of matrix producing cells during repair of bacteria induced injury in diabetic mice

Abstract

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 (TNF) 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 inhibition significantly reduced fibroblast apoptosis and caspase-3 activity in both diabetic and normoglycemic mice ([less than] 0.05).During healing etanercept reduced fibroblast apoptosis and caspase-3 activity by almost 50% in diabetic but not normoglycemic mice ([less than] 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 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. The degree of connective tissue and osseous healing stimulated in the diabetic mice by anti-TNF treatment was within the range that is physiologically relevant. This enhanced healing may in part be explained by blocking TNF induced apoptosis of critical matrix-producing cells.