NG2/CSPG4 in Mandibular Endochondral Fracture Healing
NG2/CSPG4 在下颌软骨内骨折愈合中的应用
基本信息
- 批准号:10752209
- 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:2023-09-01 至 2029-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAlkaline PhosphataseAnimal ModelBiological MarkersBiologyBone RegenerationBone callusCSPG4 geneCartilageCell Differentiation processCellsChondrocytesClinicalCollagen Type VIDataDecision MakingDegenerative polyarthritisDevelopmentEpiphysial cartilageExhibitsFractureGoalsImmunohistochemistryImpaired healingImpairmentIn VitroIncidenceInstitutionInterventionJoint structure of suture of skullKnockout MiceKnowledgeLigandsLimb structureLinkMAPK3 geneMandibleMandibular FracturesMechanicsMembraneMentorsMolecularNeckOralOsteoblastsOsteotomyOutcomeOutcome StudyPainPathway interactionsPatient-Focused OutcomesPeriosteumPhysiologic OssificationPostoperative PeriodProteoglycanQuality of lifeRegulationResearchResolutionResourcesRoleScienceScientistSignal TransductionSkeletal systemTemporomandibular JointTestingTimeTissuesTrainingTransgenic OrganismsTraumaWestern BlottingWorkbonebone fracture repaircalcificationcareer developmentcartilage cellcell injurycell typecondylar cartilagecraniofacialdesignface bone structurehealingimprovedin vivointramembranous bone formationknockout animallaboratory experimentmechanical loadmineralizationmouse modelnew therapeutic targetnovel therapeuticsosteochondral tissueosteogenicosteoprogenitor cellpre-clinicalreceptorresponseresponse to injurystem cells
项目摘要
PROJECT SUMMARY/ABSTRACT
This application represents a training plan designed to provide mentoring, career development, and support to
the applicant as a clinician-scientist seeking to move research from the benchtop to the bedside in craniofacial
and oral sciences. The training plan encompasses laboratory experimentation and professional and career
development opportunities, and the plan is supported by the outstanding local and institutional resources
available at UIC. The proposed research will address an important unmet clinical need facing craniofacial
trauma. While the mandible is the strongest and largest facial bone, there is a high level of incidence for
mandibular fractures. Unstable mandibular fractures exhibit delayed healing compared to fixed fractures, and
their healing involves a chondrocyte-to-osteoblast developmental pathway that is not yet fully understood.
Understanding the specific molecular pathways that control fracture resolution is important for improving
clinical outcomes and the development of new therapeutics. The focus of this study is on a transmembrane
proteoglycan, NG2/CSPG4. This molecule has been implicated in the mechanical response of mandibular
chondrocytes in the temporomandibular joint and the progression of osteoarthritis, but it has not been studied
in the context of endochondral fracture healing. The research plan in this proposal utilizes a preclinical murine
model of endochondral fracture healing in the mandible, together with transgenic knockout animal models, to
define the role of NG2/CSPG4 in the cell differentiation cascade that is required for the successful
mineralization of a fracture callus. The proposed research plan will test the central hypothesis that mechanical
loading-dependent NG2/CSPG4 signaling regulates the differentiation of osteochondral progenitor cells during
endochondral ossification in mandibular fractures. Long-term, our goal is to understand how cells make
decisions about their fate during bone regeneration. Aim 1 will evaluate the role of NG2/CSPG4 in the ability of
osteochondral progenitor cells to differentiate into cartilage. Aim 2 will focus on the role of NG2/CSPG4 in the
ability of cartilage cells to undergo mineralization. Together, the data generated from this project will address
an important gap in knowledge surrounding mandibular fracture healing and bone biology more broadly and
may identify a new therapeutic target for clinical intervention.
项目总结/摘要
此应用程序代表一个培训计划,旨在为以下人员提供指导、职业发展和支持
申请人作为一名临床科学家,寻求将颅面研究从台式转移到床边
口腔科学培训计划包括实验室实验和专业和职业
发展机会,该计划得到了优秀的地方和机构资源的支持
在UIC。拟议的研究将解决颅面神经外科面临的一个重要的未满足的临床需求。
外伤虽然下颌骨是最坚固和最大的面部骨骼,但
下颌骨骨折与固定骨折相比,不稳定的下颌骨骨折愈合延迟,
它们的愈合涉及软骨细胞到成骨细胞的发育途径,但目前尚未完全了解。
了解控制裂缝分辨率的特定分子途径对于改善裂缝分辨率是重要的。
临床结果和新疗法的开发。这项研究的重点是跨膜
蛋白聚糖,NG 2/CSPG 4。这种分子与下颌骨的机械反应有关
软骨细胞在颞下颌关节和骨关节炎的进展,但还没有研究
in the context背景of endochondrialfracture内骨折healing愈合.本提案中的研究计划利用临床前小鼠
下颌骨软骨内骨折愈合模型,以及转基因敲除动物模型,
确定NG 2/CSPG 4在细胞分化级联中的作用,这是成功的细胞分化所必需的。
骨折骨痂的矿化。拟议中的研究计划将检验中心假设,
负荷依赖性NG 2/CSPG 4信号调节骨软骨祖细胞的分化
下颌骨骨折中的软骨内骨化从长远来看,我们的目标是了解细胞是如何
决定他们在骨再生过程中的命运。目的1将评估NG 2/CSPG 4在以下能力中的作用:
骨软骨祖细胞分化成软骨。目标2将重点关注NG 2/CSPG 4在
软骨细胞进行矿化的能力。总之,从这个项目产生的数据将解决
更广泛地围绕下颌骨骨折愈合和骨生物学的知识存在重要差距,
可能会为临床干预确定新的治疗靶点。
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 }}
Jonathan Matthew Banks其他文献
Jonathan Matthew Banks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 }}
相似海外基金
The role of tissue nonspecific alkaline phosphatase in brain endothelial cell homeostasis
组织非特异性碱性磷酸酶在脑内皮细胞稳态中的作用
- 批准号:
10220574 - 财政年份:2021
- 资助金额:
$ 5.35万 - 项目类别:
Post-Transcriptional Processing of the Small Intestinal Alkaline Phosphatase in the Postnatal Developing Pig
产后发育猪小肠碱性磷酸酶的转录后加工
- 批准号:
RGPIN-2016-05827 - 财政年份:2021
- 资助金额:
$ 5.35万 - 项目类别:
Discovery Grants Program - Individual
The role of tissue nonspecific alkaline phosphatase in brain endothelial cell homeostasis
组织非特异性碱性磷酸酶在脑内皮细胞稳态中的作用
- 批准号:
10413987 - 财政年份:2021
- 资助金额:
$ 5.35万 - 项目类别:
The role of tissue nonspecific alkaline phosphatase in brain endothelial cell homeostasis
组织非特异性碱性磷酸酶在脑内皮细胞稳态中的作用
- 批准号:
10601067 - 财政年份:2021
- 资助金额:
$ 5.35万 - 项目类别:
Dietary induction of intestinal alkaline phosphatase intended to detoxify endotoxin and analysis of its mechanism of action.
膳食诱导肠道碱性磷酸酶解毒内毒素及其作用机制分析。
- 批准号:
20K05936 - 财政年份:2020
- 资助金额:
$ 5.35万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Selective targeting of human alkaline phosphatase isozymes
选择性靶向人碱性磷酸酶同工酶
- 批准号:
10359823 - 财政年份:2020
- 资助金额:
$ 5.35万 - 项目类别:
Functional analysis of alkaline phosphatase, a stem cell marker, using human deciduous dental pulp cells derived from the patient with Hypophosphatasia (HPP)
使用源自低磷酸酯酶症 (HPP) 患者的人乳牙牙髓细胞对干细胞标记物碱性磷酸酶进行功能分析
- 批准号:
20K10210 - 财政年份:2020
- 资助金额:
$ 5.35万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Understanding the role of tissue non-specific alkaline phosphatase in osteogenesis for the therapy of hypophosphatasia.
了解组织非特异性碱性磷酸酶在成骨作用中的作用,以治疗低磷酸酯酶症。
- 批准号:
20K16894 - 财政年份:2020
- 资助金额:
$ 5.35万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Selective targeting of human alkaline phosphatase isozymes
选择性靶向人碱性磷酸酶同工酶
- 批准号:
10117265 - 财政年份:2020
- 资助金额:
$ 5.35万 - 项目类别:
Post-Transcriptional Processing of the Small Intestinal Alkaline Phosphatase in the Postnatal Developing Pig
产后发育猪小肠碱性磷酸酶的转录后加工
- 批准号:
RGPIN-2016-05827 - 财政年份:2020
- 资助金额:
$ 5.35万 - 项目类别:
Discovery Grants Program - Individual