Neurobiological control of periodontal homeostasis through microRNA, TGF-beta, and Wnt signaling
通过 microRNA、TGF-β 和 Wnt 信号传导对牙周稳态的神经生物学控制
基本信息
- 批准号:9756189
- 负责人:
- 金额:$ 15.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-04 至 2020-02-18
- 项目状态:已结题
- 来源:
- 关键词:AffectAnimal ModelAnimalsAnkylosisBioinformaticsBiological AssayBone RegenerationBone remodelingCicatrixCollagenCytoskeletal ModelingCytoskeletal ProteinsDataData SetDefectDentitionDiagnostic radiologic examinationDown-RegulationEmotionalEngineeringEpithelialEpithelial CellsG-Protein-Coupled ReceptorsGalaninGangliaGene ExpressionGene Expression ProfilingGoalsHealthHeightHomeostasisHybridsIn VitroInterruptionJawLaboratoriesMessenger RNAMicroRNAsModelingNanosphereNerveNerve FibersNeurobiologyNeuropeptidesOperative Surgical ProceduresOsteoblastsOsteoclastsOsteocytesOsteogenesisOutcomePathway interactionsPatientsPeptidesPeriodontal DiseasesPeriodontal LigamentPeriodontal PocketPeriodontitisPeriodontiumPhenotypePreventionProteinsRattusResearchRestReverse Transcriptase Polymerase Chain ReactionRoentgen RaysRoleSensorySignal TransductionSignaling MoleculeTestingTissue EngineeringTissuesTooth AnkylosisTooth structureTransforming Growth Factor betaTrigeminal nerve structureUp-RegulationWNT Signaling PathwayWalkersalveolar bonebaseboneclinically significantcraniofacial bonedesignglycogen synthase kinase 3 betainferior alveolar nerveinhibitor/antagonistinnovationmandibular nervemineralizationnerve supplynerve transectionosteoclastogenesisosteogenicpreventprogenitorresponsesample fixationskeletogenesissoft tissuespatial relationshiptrend
项目摘要
The periodontium is a richly innervated tissue that undergoes continuous modelling and remodeling by
alveolar bone osteoblasts, osteocytes, and osteoclasts. Studies from our laboratory have demonstrated a
close spatial relationship between trigeminal nerve ganglia and the Epithelial Rests of Malassez (ERM), an
epithelial cell network residing within the non-mineralized periodontal ligament. Inferior alveolar nerve (IAN)
transection studies resulting in dento-alveolar ankylosis and a reduction in ERM have confirmed the
essential role of sensory innervation for periodontal homeostasis. For the present application, we have
established the IAN transection model in our laboratory and provided radiographic evidence for enhanced
mineralization and ankylosis in the periodontal region of rat molars. Gene expression profiling comparing
IAN transected and control tissues demonstrated an unexpected 28-fold significant increase in galanin
(GAL) and a more than two-fold decrease in the TGF-β signaling molecules Smad2, Smad3 and Tgf-β1,
and the Wnt inhibitors Dkk1, Dkk2 and Gsk-3β. In the same IAN transection group, microRNA miR-92b
expression was more than two-fold upregulated, as verified via miRNA profiling and RT-PCR. MiR-92b
upregulation after IAN transection in conjunction with bioinformatics data implicating Wnt and Tgf-β as
possible miR-92b targets prompted us to speculate that GAL affects its skeletogenic downstream effects
through miR-92b. In vitro studies revealed that GAL treatment promoted osteogenic differentiation of PDL
progenitors and increased mineralization, while reducing osteoclastogenesis of BMMCs. Block of RhoA or
application of GAL antagonist affected PDL cytoskeletal organization and gene expression, indicating that
GAL functions through G protein coupled receptors. IWhen applied to periodontal pockets of animals
suffering from periodontitis, GAL tissue engineering constructs accomplished a 20% increase in alveolar
bone levels compared to controls, resulting in a clinically significant increase in alveolar bone height. Based
on this promising new set of data we have designed a research plan to define the role of GAL in response
to IAN transection, determine the mechanism underlying its effect on skeletogenesis, and exploit its
applicability for bone regeneration and the prevention of periodontal ankylosis. The overall goal of our
research plan is to test the hypothesis that periodontal nerves affect alveolar bone homeostasis
through a GAL–GPCR–miR-92b–TGF-β/Wnt regulatory loop and that application of GAL
neurosecretory peptides will stimulate Wnt signaling and new bone formation. We anticipate that the
outcomes of our study will lead to innovative neuropeptide based/engineering hybrid approaches that will
restore periodontal health in millions of patients and prevent the emotional and functional scars associated
with lost teeth and incomplete dentitions.
牙周组织是一个神经支配丰富的组织,它经历了持续的塑造和重塑
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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Tom Diekwisch其他文献
Tom Diekwisch的其他文献
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{{ truncateString('Tom Diekwisch', 18)}}的其他基金
Small molecule mediated restoration of periodontal homeostasis through the YAP1 pathway
小分子通过 YAP1 途径介导牙周稳态恢复
- 批准号:
10869312 - 财政年份:2023
- 资助金额:
$ 15.39万 - 项目类别:
Ameloblast Differentiation and Amelogenesis: Next-Generation Models to Define Key Mechanisms and Factors Involved in Biological Enamel Formation
成釉细胞分化和成釉细胞:定义生物牙釉质形成涉及的关键机制和因素的下一代模型
- 批准号:
10874800 - 财政年份:2023
- 资助金额:
$ 15.39万 - 项目类别:
Ameloblast Differentiation and Amelogenesis: Next-Generation Models to Define Key Mechanisms and Factors Involved in Biological Enamel Formation
成釉细胞分化和成釉细胞:定义生物牙釉质形成涉及的关键机制和因素的下一代模型
- 批准号:
10416108 - 财政年份:2021
- 资助金额:
$ 15.39万 - 项目类别:
Ameloblast Differentiation and Amelogenesis: Next-Generation Models to Define Key Mechanisms and Factors Involved in Biological Enamel Formation
成釉细胞分化和成釉细胞:定义生物牙釉质形成涉及的关键机制和因素的下一代模型
- 批准号:
10460290 - 财政年份:2021
- 资助金额:
$ 15.39万 - 项目类别:
Neurobiological control of periodontal homeostasis through microRNA, TGF-beta, and Wnt signaling
通过 microRNA、TGF-β 和 Wnt 信号传导对牙周稳态的神经生物学控制
- 批准号:
10112718 - 财政年份:2020
- 资助金额:
$ 15.39万 - 项目类别:
Small molecule mediated restoration of periodontal homeostasis through the YAP1 pathway
小分子通过 YAP1 途径介导牙周稳态恢复
- 批准号:
9892878 - 财政年份:2017
- 资助金额:
$ 15.39万 - 项目类别:
Small molecule mediated restoration of periodontal homeostasis through the YAP1 pathway
小分子通过 YAP1 途径介导牙周稳态恢复
- 批准号:
9311559 - 财政年份:2017
- 资助金额:
$ 15.39万 - 项目类别:
Enamel Structure Sophistication throuth Amelogenin Evolution
牙釉质结构通过牙釉蛋白进化而变得复杂
- 批准号:
7840703 - 财政年份:2009
- 资助金额:
$ 15.39万 - 项目类别:
Enamel Structure Sophistication throuth Amelogenin Evolution
釉原蛋白进化带来的复杂牙釉质结构
- 批准号:
7880098 - 财政年份:2008
- 资助金额:
$ 15.39万 - 项目类别:
Enamel Structure Sophistication throuth Amelogenin Evolution
牙釉质结构通过牙釉蛋白进化而变得复杂
- 批准号:
7527401 - 财政年份:2008
- 资助金额:
$ 15.39万 - 项目类别:
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