Wnt5a/Ror2 Signaling in Jaw Bone Development
颌骨发育中的 Wnt5a/Ror2 信号转导
基本信息
- 批准号:10730208
- 负责人:
- 金额:$ 3.22万
- 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:2023-01-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAnimalsAutomobile DrivingBirdsBone DevelopmentBone GrowthBone RegenerationBone ResorptionBone Resorption InhibitionBone Resorption StimulationBreathingCa(2+)-Calmodulin Dependent Protein KinaseCalciumCell LineCellsCephalicComplexCongenital AbnormalityCraniofacial AbnormalitiesDataDefectDepositionDevelopmentDiseaseDisparityDistraction OsteogenesisDucksElementsEmbryoEndowmentEnzymesEventFaceFamily memberFutureGene ExpressionGene Expression ProfilingGenesGoalsGrowth and Development functionHumanHyperplasiaInhibition of Matrix Metalloproteinases PathwayInjuryInterventionJawKnowledgeLaboratoriesMMP9 geneMandibleMasticationMaxillaMediatingMolecularMusMutationNeural CrestOperative Surgical ProceduresOrphanOsteoblastsOsteoclastsOsteocytesPatternPlayPopulationProceduresProcessQuailQuality of lifeReceptor Protein-Tyrosine KinasesRegulationRobinow syndromeRoleShapesSignal InductionSignal TransductionSkeletonStructureTRANCE proteinTechniquesTestingTissuesTransplantationTransplantation ChimeraTumor necrosis factor receptor 11bWestern BlottingWorkbisphosphonatebonecalmodulin-dependent protein kinase IIcathepsin Kcell typecollagenase 3craniofacial developmentcraniofacial structureface bone structuregain of functiongenetic technologyin vivoknock-downknowledge baselong boneloss of functionmalformationmembermultiphoton microscopynovelnovel therapeuticsosteogenicoverexpressionplanar cell polaritypreventprogramsreceptorrepairedtomographytransplant modeltreatment strategy
项目摘要
PROJECT SUMMARY
Our long-term goal is to discover novel molecular-based therapies for regulating the size of bone as a means to
address the need for non-surgical treatments of craniofacial malformations. Little is known regarding the precise
molecular mechanisms controlling jaw size during growth and development. This lack of knowledge leaves
distraction osteogenesis as one of the few available interventions to change jaw size, even though bones of the
face are known to be much more difficult to manipulate with this technique than long bones. Procedures to treat
jaw size disparities will greatly benefit from a broader knowledge base of molecular and cellular mechanisms
that control jaw size. The objective of the current study is to build toward this goal by understanding how the
cranial neural crest (CNC), which forms all the elements in the facial and jaw skeletons, regulates jaw size. To
address this issue, we propose to manipulate in vivo the CNC, a highly accessible embryonic population. For
example, we can transplant quail donor CNC into a duck host, which creates a chimeric quck; and we transplant
duck donor CNC into the quail host, generating chimeric duail. Exploiting the divergent developmental programs
of quail and duck provides a unique way to manipulate signaling between CNC and adjacent host tissues and
allows discovery of CNC-dependent processes. Some groups have looked at bone deposition in controlling jaw
size, but our data suggest that bone resorption by mesodermally-derived osteoclasts with participation of CNC-
derived osteocytes control jaw size at later stages of development. We have previously shown that CNC controls
jaw size, bone resorption is controlled by CNC and that bone resorption controls jaw size. How CNC
accomplishes such a complex task, and what factors are sufficient to replicate this phenomenon, is unknown.
Likely candidates may include members and targets of WNT5A/ROR2 noncanonical signaling, since they are
known to play critical roles during bone resorption. Therefore, we hypothesize that by modulating WNT5A/ROR2
non-canonical signaling, CNC directs bone resorption to control jaw bone size. To test our hypothesis, we
propose two complementary and highly translational Specific Aims. Specific Aim 1 will determine the mechanism
by which CNC-derived osteocytes and mesodermally-derived osteoclasts act via WNT5A/ROR2 non-canonical
signaling to resorb bone and regulate jaw bone size. Specific Aim 2 will determine the mechanism via which
CNC acts by WNT5A/ROR2 noncanonical signaling to regulate the actions of osteoclast-mediated bone
resorption to regulate jaw bone size. We will employ gain- and loss-of-function techniques to identify molecular
mechanisms that endow CNC with the ability to control mandibular bone development. By determining the
precise mechanism of control of bone resorption by osteoclasts and osteocytes, future studies will be able to
develop accurate therapies to control lower jaw bone development.
项目总结
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Treatment with an inhibitor of matrix metalloproteinase 9 or cathepsin K lengthens embryonic lower jaw bone.
使用基质金属蛋白酶 9 或组织蛋白酶 K 抑制剂进行治疗可延长胚胎下颌骨。
- DOI:10.1111/ocr.12635
- 发表时间:2023
- 期刊:
- 影响因子:3.1
- 作者:Houchen,ClaireJ;Castro,Bethany;HahnLeat,Portia;Mohammad,Nashwa;Hall-Glenn,Faith;Bumann,ErinE
- 通讯作者:Bumann,ErinE
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Erin Ealba Bumann其他文献
Erin Ealba Bumann的其他文献
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{{ truncateString('Erin Ealba Bumann', 18)}}的其他基金
Wnt5a/Ror2 Signaling in Jaw Bone Development
颌骨发育中的 Wnt5a/Ror2 信号转导
- 批准号:
10545297 - 财政年份:2022
- 资助金额:
$ 3.22万 - 项目类别:
Wnt5a/Ror2 Signaling in Jaw Bone Development
颌骨发育中的 Wnt5a/Ror2 信号转导
- 批准号:
10353862 - 财政年份:2021
- 资助金额:
$ 3.22万 - 项目类别:
Wnt5a/Ror2 Signaling in Jaw Bone Development
颌骨发育中的 Wnt5a/Ror2 信号转导
- 批准号:
10669478 - 财政年份:2021
- 资助金额:
$ 3.22万 - 项目类别:
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