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UBC Theses and Dissertations

Experimental diabetes in ß6 integrin deficient mice Aurora, Saljae


Objectives: Periodontal disease involves transformation of the junctional epithelium (JE) to a pocket epithelium (PE). Integrin avß6 is constitutively expressed in the healthy IF but not in PE. Mice deficient of this integrin (ß6-/-) exhibit increased periodontal bone loss and PE migration. Thus, avß6 integrin in JE may have a protective role against periodontal disease. As diabetes aggravates periodontal disease, we hypothesized that diabetic ß6-/- mice would develop more advanced periodontal disease compared to nondiabetic mice. Furthermore, we hypothesize that re-introduction of ß6 integrin under the cytokeratin 14 (Ki 4) gene promoter in the ß6-/- strain, would restore protection against periodontal disease. Methods: Wild-type (WIT), ß6-/-, ß6 integrin over-expressing (Kl4ß6; ß6 integrin expression is driven by Ki 4 promoter) and ß6 integrin rescue (ß6-rescue; cross-breed of ß6-/- and K14ß6 mice) mice were induced to develop diabetes by injections of streptozotocin, and confirmed diabetic 2 weeks later (Blood glucose >306 mg/dl (17 mmollL). Control animals were exposed to the citrate vehicle only. Four months later, mice were sacrificed. Mandibles were dc-fleshed and imaged for quantification of periodontal bone loss. Maxillae were decalcified and sectioned for histological assessment of epithelial migration and inflammation. Results: Diabetic ß6-/- mice (71% mortality) exhibited significantly higher death rates as compared to non-diabetic WT and K14ß6 groups. Epithelial migration for the ß6-/- strain was significantly higher than that seen in the W/T and the K14ß6 strains. (P<0.001). Significantly reduced epithelial migration was noted for the ß6 Rescue strain compared to ß6-/- strain. Periodontal bone loss was significantly greater in the male ß6-/- strain when combined with experimental diabetes (P<O.05), while experimental diabetes did not increase alveolar bone loss in other male groups. Female diabetic mice appear protected from alveolar bone loss. Inflammation was significantly greater for both the ß6 Rescue strain and ß6-/- strain relative to the W/T strain. Conclusions: Integrin avß6 protects diabetic animals from death and periodontal disease. Reductions in epithelial migration and mortality in the ß6 Rescue strain reinforce the role of avß6 integrin in suppressing inflammation. Diabetes can aggravate periodontal bone loss in male diabetic ß6-/- mice.

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