Topical Vitamin D and Periodontal Disease
外用维生素 D 与牙周病
基本信息
- 批准号:10600091
- 负责人:
- 金额:$ 46.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-02 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalActinobacillus actinomycetemcomitansAddressAffectAnti-Bacterial AgentsApicalBacteriaBioinformaticsBone DevelopmentBone ResorptionCalciumCellsCholecalciferolChronicClinicalClinical TrialsComplexDataDevelopmentEpigenetic ProcessEpithelial CellsEpitheliumFeedbackGenesGeneticGingivaGrowthHealthHealth StatusHomeostasisHost DefenseHumanImmuneImmunityIn VitroInflammationInflammation MediatorsInflammatoryInflammatory ResponseInflammatory Response PathwayKineticsLinkMechanicsMediatingMixed Function OxygenasesMolecularMusNatural ImmunityOperative Surgical ProceduresOralOral cavityOutcomePathway interactionsPeptidesPeriodontal DiseasesPeriodontitisPopulationPorphyromonas gingivalisPreventive therapyProductionPublishingRegulationReportingRoleSignal PathwaySurfaceTissuesTooth LossTopical applicationToxic effectVitamin DVitamin D DeficiencyVitamin D supplementationVitamin D3 ReceptorVitaminsabsorptionantimicrobialbone losscathelicidin antimicrobial peptidecommensal microbescytokinecytotoxicitydysbiosismouse modeloral cavity epitheliumoral infectionoral microbial communityoral microbiomeoral supplementationpathogenic bacteriaperiodontopathogenpreventresponsesupervitaminosisthree dimensional cell culturetranscription factor
项目摘要
PROJECT SUMMARY/ABSTRACT
Periodontal disease is associated with an increase in Porphyromonas gingivalis, dysbiosis of the commensal
microbiota in the subgingival crevice, and chronic inflammation resulting in bone resorption, and ultimately tooth
loss. Vitamin D is best known as a principal factor that maintains calcium homeostasis and is required for bone
development and homeostasis. However, it is becoming clear that vitamin D has profound actions in immunity
and inflammation as well. Both the chronic and aggressive forms of periodontal disease have been associated
with vitamin D deficiency in numerous populations. Our recently published data show that the active form of
vitamin D, 1,25(OH)2D3, promotes anti-bacterial activity against P. gingivalis by gingival epithelial cells (GEC),
and inhibits pro-inflammatory cytokine expression. Experimental vitamin D deficiency in mice leads to gingival
inflammation and bone loss. However, clinical trials examining the effect of oral vitamin D supplementation on
periodontal disease have led to conflicting results, likely due to natural feedback mechanisms. We therefore
hypothesized that topical administration of vitamin D to the gingiva could circumvent this problem. Our
preliminary results indicate that when inactive vitamin D is delivered directly to the surface of the gingival
epithelium, both in vitro and in mice, we observe a rapid induction of vitamin D-mediated genes, as well as an
inhibition of pro-inflammatory cytokines, without cytotoxicity. We also observed that the epithelial cells convert
inactive vitamin D3 to both the inactive intermediate (25OHD3), and to active 1,25(OH)2D3 through epithelial cell-
expressed hydroxylases, and that this conversion resulted in increased production of the host defense peptide,
LL-37. Thus, our overarching hypothesis is that that the gingival epithelium maintains its own intrinsic regulation
of vitamin D status, and that topical delivery of vitamin D to the oral epithelium allows direct introduction of high
concentrations of active vitamin D to the tissue. This delivery can lead to regulation of vitamin D-regulated genes
that can downregulate inflammation and prevent the growth of periopathogenic bacteria, and the resulting bone
loss. To address this, we propose the following specific aims: 1) Quantify the relationship between vitamin D
and periodontal disease in a mouse model. 2) Define the shifts in the oral microbiome regulated by
vitamin D. 3) Characterize the mechanism of vitamin D-mediated induction of innate immunity in cultured
human GEC. Together, these aims will support our hypothesis that vitamin D is essential for periodontal health,
will help define the mechanism by which this occurs, and will provide a proof of principle that topical
administration of vitamin D in the oral cavity can maintain this health status. Vitamin D’s actions are complex and
multifaceted, but harnessing its beneficial activities has the potential to change periodontal practice replacing
expensive mechanical and surgical procedures with well-reasoned, safe and reliable topical treatments with no
toxicity.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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GILL DIAMOND其他文献
GILL DIAMOND的其他文献
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{{ truncateString('GILL DIAMOND', 18)}}的其他基金
Initiation of immune responses to SARS COV2 in the oral cavity and upper airway
在口腔和上呼吸道启动针对 SARS COV2 的免疫反应
- 批准号:
10990201 - 财政年份:2023
- 资助金额:
$ 46.23万 - 项目类别:
Initiation of immune responses to SARS COV2 in the oral cavity and upper airway
在口腔和上呼吸道启动针对 SARS COV2 的免疫反应
- 批准号:
10446223 - 财政年份:2022
- 资助金额:
$ 46.23万 - 项目类别:
Initiation of immune responses to SARS COV2 in the oral cavity and upper airway
在口腔和上呼吸道启动针对 SARS COV2 的免疫反应
- 批准号:
10579342 - 财政年份:2022
- 资助金额:
$ 46.23万 - 项目类别:
Antimicrobial peptide mimetic activity against Candida auris
针对耳念珠菌的抗菌肽模拟活性
- 批准号:
10369013 - 财政年份:2021
- 资助金额:
$ 46.23万 - 项目类别:
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