Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis) in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed.

Wnt proteins are intercellular signals that regulate various aspects of animal development. In Caenorhabditis elegans, mutations in lin-17, a Frizzled-class Wnt receptor, and in lin-18 affect cell fate patterning in the P7.p vulval lineage. We found that lin-18 encodes a member of the Ryk/Derailed family of tyrosine kinase-related receptors, recently found to function as Wnt receptors. Members of this family have nonactive kinase domains. The LIN-18 kinase domain is dispensable for LIN-18 function, while the Wnt binding WIF domain is required. We also found that Wnt proteins LIN-44, MOM-2, and CWN-2 redundantly regulate P7.p patterning. Genetic interactions indicate that LIN-17 and LIN-18 function independently of each other in parallel pathways, and different ligands display different receptor specificities. Thus, two independent Wnt signaling pathways, one employing a Ryk receptor and the other a Frizzled receptor, function in parallel to regulate cell fate patterning in the C. elegans vulva.

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Background: There is no cure for autoimmune chronic inflammatory bowel disease (IBD). IBD patients commonly use complementary and alternative medications of which the safety, efficacy, and interaction with standard-of-care therapies are not fully known. Thus the consequences can become life-threatening. Sulfasalazine commonly used in IBD, potentially has severe adverse effects, including infertility, pulmonary fibrosis, lack of response, and ultimately patients may require intestinal resection. We hypothesized that green tea polyphenols (GrTP, EGCG) and sulfasalazine have similar anti-inflammatory properties.Methods: BALB/c mice received Dextran sodium sulfate (DSS) to induce colitis (ulcerative colitis model). Exposure of IL-10 deficient mice (BALB/c-background) to normal microbiota provoked enterocolitis (mimics Crohn’s disease). Animals were treated with agents incorporated into daily diets. Control animals received sham treatment.Results: DSS-treated animals developed severe bloody diarrhea and colitis (score 0–4, 3.2 ± 0.27). IL-10 deficient mice developed severe enterocolitis as manifested by diarrhea, rectal prolapse, and colonic lesions. Animals tolerated regimens (GrTP, EGCG, sulfasalazine) with no major side effects, and further developed less severe colitis. IL-10 deficient animals became moribund on high dose, while tolerated low and Mid doses with significant improved symptoms of enterocolitis. GrTP, EGCG, and sulfasalazine significantly ameliorated colonic damage and histological scores in treated animals in a similar manner (GrTP vs. DSS p < 0.05; EGCG, sulfasalazine vs. DSS p < 0.01). The inflammatory markers TNFα (3-fold), IL-6 (14-fold), and serum amyloid A (40-fold) increased in colitic animals and significantly decreased with treatment regiments. In contrast, circulatory leptin levels decreased in colitic animals (twofold). EGCG additionally reduced leptin levels (p < 0.01) while GrTP and sulfasalazine had no effect on leptin levels (p < 0.05). Hepatic and colonic antioxidants were significantly depleted in colitic animals and treatment regiments significantly restored antioxidants levels.Conclusion: GrTP and EGCG improved antioxidants levels and attenuated severity of colitis analogous to sulfasalazine. Future studies will reveal whether polyphenols can become an alternative/additive therapy for IBD therapy in humans.