Gingival Fibroblast and Epithelial Functions in Periodontal Disease-Modulation by Insulin Resistance Public Deposited

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  • June 7, 2019
  • Yu, Ning
    • Affiliation: School of Dentistry, Oral and Craniofacial Biomedicine PhD Program
  • Periodontal disease is a biofilm-initiated inflammatory condition that affects the tooth supporting apparatus. Gingival epithelium provides an early line of defense against bacteria while gingival connective tissue fibroblast plays an integral role in tissue remodeling and host responses. Therefore, investigating the alterations of gingival fibroblast and epithelial functions in periodontal disease improves our understandings about disease pathogenesis. In addition, both cells need energy support to survive and act, which come from glucose utilization that is profoundly influenced by insulin response and glucose metabolism. In the second chapter, we find that acute gingival inflammation markedly induces insulin response genes. However, these changes are not evident in chronic inflammation. This study suggests that acute gingival inflammation may induce tissue metabolism which could contributes to the pathogenesis of periodontal disease. In the third chapter, we find that AGEs inhibit gingival fibroblast migration. In addition to that, lipopolysaccharides (LPS) potently induce PTGS2 and MMP1 genes transcription and prior exposures to AGEs enhance the up-regulation. LPS or AGEs fail to induce FGF2, which is an anabolic growth factor. This study links AGEs with accelerated periodontium destruction and impaired gingival wound healing during diabetic periodontitis. In the fourth chapter, we seek to unravel the role of desmosome structural molecule plakophilin-2 (PKP2) in periodontal disease. Decreased epithelial PKP2 is associated with periodontitis in gingival biopsy samples. Porphyromonas gingivalis (P.g) specifically degrade PKP2 protein through cysteine proteases, not serine proteases, or intracellular proteasomal or lysosomal degradation pathways. Although in vitro stimulations of P.g increase the overall PKP2 DNA methylation level, periodontitis gingival biopsies do not demonstrate differential DNA methylation patterns compared to healthy biopsies. Gingival epithelial cells that lack PKP2 have inhibited cell proliferation, cell spreading, and impaired cell permeability. This chapter provides innovative evidence about the association between dampened desmosome molecules and periodontal disease. In summary, this dissertation work deepens our knowledge about the pathogenesis of periodontal disease from both tissue and cellular levels.
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Rights statement
  • In Copyright
  • Barros, Silvana
  • Everett, Eric
  • Khan, Asma
  • Liu, Zhi
  • Offenbacher, Steven
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2015
Place of publication
  • Chapel Hill, NC
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