The Role of Bone Sialoprotein in Modulating Periodontal Development and Repair
骨唾液酸蛋白在调节牙周发育和修复中的作用
基本信息
- 批准号:10752141
- 负责人:
- 金额:$ 5.35万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-01 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:AblationAddressAdhesionsAdultAffectAgeBindingBiologyBite ForceBone ResorptionBone remodelingCell-Matrix JunctionCellsCementoblastCementogenesisCephalicClinicalCollagenComplexCoupledCouplingDataDefectDental CementumDentitionDevelopmentDiseaseDisease ProgressionEnsureEpithelial CellsEpitheliumExhibitsExtracellular Matrix ProteinsFutureGene ExpressionGenesGingivaGoalsHealthHeightHomeostasisHydroxyapatitesImpairmentInfectionInflammationIntegrin BindingInterpersonal RelationsInvadedKnockout MiceKnowledgeMapsMicrobeModelingMolecularMusNeural CrestOralOral cavityOsteoblastsOsteoclastsOsteoporoticOvariectomyPatientsPeriodontal DiseasesPeriodontal LigamentPeriodontiumPhenotypePopulationPostmenopausal OsteoporosisPostmenopauseProcessProteinsResearchRodent ModelRoleSerumSkeletonSourceSymptomsTestingTherapeuticTissuesTooth ExtractionTooth LossTooth structureUnited StatesWorkalveolar bonebone healingbone metabolismbone sialoproteincraniofacialedentulismexperimental studyhealingimprovedinsightmineralizationnovelpreventrepairedself esteemskeletal tissue
项目摘要
Project Summary
In the United States, 47% of adults 30 years or older are affected by periodontal disease, and this rate
increases with age to 70% in adults 65 years or older. The periodontal complex, consisting of alveolar bone,
cementum, gingiva, and the periodontal ligament (PDL), works to ensure proper tooth attachment and
nourishment, distribute occlusal forces, maintain alveolar bone height, and protect the periodontium from
invading microbes. Periodontal disease leads to the destruction of one or more of these tissues, which
ultimately results in partial or total edentulism as well as reduced function of the masticatory complex, self-
esteem, and interpersonal relationships. Most therapies are unpredictable as well as unsuccessful at repairing
all three lost or damaged tissues. Bone sialoprotein (Ibsp gene; BSP protein) is a multifunctional, extracellular
matrix protein found in mineralized tissues of the skeleton and dentition, including alveolar bone and
cementum. Total knockout mice (Ibsp-/-) display reduced acellular cementum, hypomineralized alveolar bone,
PDL detachment, severe alveolar bone resorption, tooth loss, and periodontal destruction. To date, nearly all
studies on BSP focus on its roles in cranial and postcranial development. However, its dual functions in
osteoblasts and osteoclasts also suggest an important role in the coupled process of bone remodeling; Ibsp-/-
mice show dramatic defects in alveolar bone socket healing following molar extraction. While the importance of
BSP in the periodontal complex is evident, its molecular functions remain unclear. We propose BSP is a key
molecule in periodontal development, homeostasis, and repair. The outlined experiments will test our central
hypothesis that BSP modulates periodontal development and repair through its functions in key cells for
periodontal function: cementoblasts, osteoblasts, and osteoclasts. The overall objectives of this proposal are:
1.) define the origin of BSP and cementoblast lineage using conditional ablation of Ibsp from ectomesenchymal
vs. epithelial cell populations; 2.) elucidate the role(s) of BSP in osteoblast and osteoclast function(s) in
alveolar bone healing by conditionally ablating Ibsp from osteoblasts and osteoclasts; and 3.) determine the
role of BSP in postmenopausal osteoporotic changes to bone metabolism using an ovariectomy (OVX) rodent
model of postmenopausal osteoporosis. The knowledge gained from this proposal holds promise for the
development of novel and reparative therapies of the periodontal complex. Successful completion of the
proposed research will provide key insights into the function(s) of BSP in periodontal biology as well as
diseases characterized by excessive osteoblast-osteoclast decoupling.
项目总结
项目成果
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