To study the role of TNF inhibitor in altering apoptosis of matrix producing cells during repair of bacteria induced injury in diabetic mice
Bal, Harbinder Singh
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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.
PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact firstname.lastname@example.org.Thesis (MSD)--Boston University Goldman School of Dental Medicine, 2007 (Department of Periodontology and Oral Biology).Includes bibliographical references: leaves 59-68.
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