Periodontal disease, characterized by destruction of periodontal tissues, is more prevalent and severe in patients with diabetes as compared to those without diabetes. Although it is known that matrix metalloproteinases (MMPs) and inflammatory cytokines play a critical role in destructive periodontal disease, the periodontal expression of MMPs and cytokines in diabetic patients has not been elucidated and compared to that in nondiabetic patients. Furthermore, it is not clear how diabetes-associated pathogenic factors such as hyperglycemia interplay with bacterial virulence factors to promote periodontal tissue destruction. Recently, we found that long-term pre-exposure of U937 histiocytes and human monocyte-derived macrophages to high glucose 25 mM) markedly augments lipopolysaccharide (LPS)- stimulated MMP and cytokine expression when compared to pre-exposure to normal glucose 5 mM), suggesting that a synergism between hyperglycemia and the bacterial virulence factor may enhance the periodontal expression of MMPs and cytokines in diabetic patients. In this research project, we have two Specific Aims: First, we will further determine the signaling and molecular mechanisms involved in the synergisms between high glucose and IPS on MMP and cytokine expression. We posit that high glucose augments MMP and cytokine expression by enhancing LPS-activated signaling pathways. Second, we will illustrate the periodontal expression of MMPs and cytokines in diabetic and nondiabetic patients, and establish a relationship between diabetes and periodontal expression of MMPs and cytokines. We postulate that periodontal expression of MMPs and cytokines is associated with hyperglycemia. In this research project, we will use protein and DMA arrays and other new techniques, and combine basic research with patient study. The novel information obtained from this study will elucidate the potential targets for the therapeutic intervention of diabetes-associated periodontal disease. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE016353-02
Application #
7094102
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lumelsky, Nadya L
Project Start
2005-07-15
Project End
2010-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
2
Fiscal Year
2006
Total Cost
$304,741
Indirect Cost
Name
Medical University of South Carolina
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Li, Guang; Robles, Samantha; Lu, Zhongyang et al. (2018) Upregulation of free fatty acid receptors in periodontal tissues of patients with metabolic syndrome and periodontitis. J Periodontal Res :
Jin, Junfei; Lu, Zhongyang; Li, Yanchun et al. (2018) LPS and palmitate synergistically stimulate sphingosine kinase 1 and increase sphingosine 1 phosphate in RAW264.7 macrophages. J Leukoc Biol 104:843-853
Lu, Z; Li, Y; Brinson, C W et al. (2017) CD36 is upregulated in mice with periodontitis and metabolic syndrome and involved in macrophage gene upregulation by palmitate. Oral Dis 23:210-218
Lu, Zhongyang; Li, Yanchun; Brinson, Colleen W et al. (2017) Cooperative stimulation of atherogenesis by lipopolysaccharide andĀ palmitic acid-rich high fat diet in low-density lipoprotein receptor-deficient mice. Atherosclerosis 265:231-241
Poston, C J; Pierce, T C; Li, Y et al. (2016) Statin intake is associated with MMP-1 level in gingival crevicular fluid of patients with periodontitis. Oral Dis 22:438-44
Brinson, Colleen W; Lu, Zhongyang; Li, Yanchun et al. (2016) Lipopolysaccharide and IL-1? coordinate a synergy on cytokine production by upregulating MyD88 expression in human gingival fibroblasts. Mol Immunol 79:47-54
Lu, Zhongyang; Li, Yanchun; Jin, Junfei et al. (2015) GPR40/FFA1 and neutral sphingomyelinase are involved in palmitate-boosted inflammatory response of microvascular endothelial cells to LPS. Atherosclerosis 240:163-73
Lu, Zhongyang; Zhang, Xiaoming; Li, Yanchun et al. (2015) TLR4 antagonist attenuates atherogenesis in LDL receptor-deficient mice with diet-induced type 2 diabetes. Immunobiology 220:1246-54
Mize, T W; Sundararaj, K P; Leite, R S et al. (2015) Increased and correlated expression of connective tissue growth factor and transforming growth factor beta 1 in surgically removed periodontal tissues with chronic periodontitis. J Periodontal Res 50:315-9
Li, Y; Lu, Z; Zhang, X et al. (2015) Metabolic syndrome exacerbates inflammation and bone loss in periodontitis. J Dent Res 94:362-70

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