Rspondin-Lgr Axis in Bone Regeneration
骨再生中的 Rspondin-Lgr 轴
基本信息
- 批准号:10469469
- 负责人:
- 金额:$ 37.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-10 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdultAttenuatedBMP2 geneBindingBone InjuryBone RegenerationBone callusCalvariaCell LineageCellsChondrocytesClinicalDataDefectDevelopmentEmbryoFamilyFamily memberFractureGPR4 geneGenesGoalsHandHistologyIn VitroIncidenceIndividualInjuryKnockout MiceLeadLeucine-Rich RepeatLigandsLimb DevelopmentLimb structureLoxP-flanked alleleMechanicsMesenchymalMesenchymal Stem CellsMesenchymeMineralsModelingMolecularMolecular AnalysisMusOsteoblastsOsteogenesisPathway interactionsPeriosteal CellPeriosteumPlayPositioning AttributeProcessPropertyProteinsPublic HealthPublishingReceptor SignalingRecombinantsRegulationReporterResearchRoleSignal TransductionSiteSkeletal DevelopmentTestingTherapeutic UsesTimeWNT Signaling Pathwaybasebonebone fracture repairbone healingbone repaircraniofacialhealingin vivoinjuredlong bonemRNA ExpressionmicroCTmouse modelnovelnovel strategiesnovel therapeuticsosteoblast differentiationosteochondral tissueosteogenicosteoprogenitor cellpreventprogenitorprotein functionreceptorregenerative therapyresponseresponse to injuryskeletalstemstem cellstissue regeneration
项目摘要
There is an urgent clinical need to develop new therapeutics to promote bone regeneration. A
critical aspect of the bone healing process begins with the expansion of periosteal progenitors
that occurs immediately after injury and then the differentiation of these progenitors to bone
forming osteoblasts and chondrocytes, yet mechanisms that control skeletal progenitor/stem cell
activation, expansion, and differentiation in response to injury are poorly described. Our project
will study the role of the R-spondin (ligand) – Lgr (receptor) signaling axis in regulating these
progenitors and bone regeneration. R-spondins (roof plate specific spondin) are a family of four
secreted matricellular proteins (Rspo1-4) that bind to Leucine-rich repeat-containing G-protein
coupled receptors 4/5/6 (Lgrs). Rspo-Lgr interaction potentiate canonical Wnt pathway by
preventing the turnover of Wnt Frizzled receptors, and hence determines canonical Wnt
signaling levels. While canonical Wnt signaling is known to play an important role in bone
regeneration, very little research has explored positive modulators of Wnt signaling. In
particular, the requirement of Rspo-Lgr in the context of fracture healing has never been
examined due to lack of appropriate models. Our primary goal is to define the requirement of
Rspo2/3 and Lgr6 in mesenchymal progenitors in response to bone injury. We have defined
three specific aims to address this goal. In Aim1, we will use single and compound Rspo2 and
Rspo3 floxed mice crossed with an alphaSMACreERT2 mouse to disrupt the Rspo2/3 genes in
mesenchymal progenitors at the time of fracture. Bone healing will be assessed using microCT,
histology, molecular analysis, and mechanical testing. Alterations in canonical Wnt signaling
and osteogenic potential of Rspo2/3 deficient progenitors will be assessed. In Aim 2, Lgr6
knockout mice will be investigated for their bone healing properties using parameters similar to
Aim 1. In Aim 3, Rspo2 will be delivered to bone injury sites and the impact on BMP and Wnt
signaling, progenitor activation and differentiation, and bone healing assessed. Completion of
this project will identify the requirement of Rspo2/3-Lgr6 interaction in fracture healing and will
provide new therapeutic directions for enhancing bone healing.
临床迫切需要开发新的治疗方法来促进骨再生。一个
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Kurt David Hankenson其他文献
Kurt David Hankenson的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Kurt David Hankenson', 18)}}的其他基金
FASEB SRC: Matricellular Proteins: Fundamental Concepts and New Directions
FASEB SRC:基质细胞蛋白:基本概念和新方向
- 批准号:
10468385 - 财政年份:2022
- 资助金额:
$ 37.94万 - 项目类别:
ORS-ISFR 17th Biennial Conference: Thinking big on fracture repair
ORS-ISFR 第 17 届双年会:对骨折修复的大思考
- 批准号:
10066004 - 财政年份:2020
- 资助金额:
$ 37.94万 - 项目类别:
BMP6 Induction of Human Mesenchymal Stem Cell Osteoblast Differentiation
BMP6 诱导人间充质干细胞成骨细胞分化
- 批准号:
7436259 - 财政年份:2006
- 资助金额:
$ 37.94万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 37.94万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 37.94万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 37.94万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 37.94万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 37.94万 - 项目类别:
Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 37.94万 - 项目类别:
Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
- 批准号:
10065645 - 财政年份:2023
- 资助金额:
$ 37.94万 - 项目类别:
Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 37.94万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 37.94万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 37.94万 - 项目类别:
Grant-in-Aid for Scientific Research (C)