Regulation of tendon development by CCN1/Cyr61
CCN1/Cyr61 对肌腱发育的调节
基本信息
- 批准号:9319576
- 负责人:
- 金额:$ 16.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-03-10 至 2018-12-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAgeAlpha CellAnterior Cruciate LigamentBehaviorCartilageCell ProliferationCellsCharacteristicsCicatrixCongenital AbnormalityCongenital clubfootDataDefectDeformityDevelopmentDiseaseEngineeringExhibitsExtracellular MatrixFamilyFibroblastsFibrosisFutureGaitGene ExpressionGene Expression ProfileHistologicIn VitroInferiorLigamentsLimb structureMaintenanceMechanicsMolecularMusMuscleMusculoskeletal SystemPathway interactionsPhenotypePlayProteinsRecurrenceRegulationRoleStem cellsTendon InjuriesTendon structureTestingTherapeuticTherapeutic AgentsTherapeutic UsesThickTissuesachilles tendonbonecommon treatmentexpectationflexibilityhealingin vivoinjury and repairmechanical propertiesmembermutantpatellar tendonpostnatalpreventprogenitorsenescencesuccesstendon developmenttranscriptome sequencingwound
项目摘要
PROJECT SUMMARY
The mechanisms underlying tendon development are by far the least understood of any component of the
musculoskeletal system. This is a concern because tendon injuries are common and treatment options are
limited. Healing often results in formation of scar tissue, which is compositionally and mechanically inferior to
native tendon, resulting in decreased flexibility and a high recurrent tear rate. Members of the CCN family of
matricellular proteins have been extensively studied due to their key roles in multiple fibrotic conditions, but
their roles in normal fibrous tissues like tendons are unknown. We found that CCN1/Cyr61 s highly expressed
in tendon and ligament, and that mice in which Ccn1 is ablated in tendon/ligament progenitor stem cells
(TPSCs) using Scx-Cre (Ccn1SKO) exhibit a clubfoot-like phenotype. Histological analysis revealed that anterior
cruciate ligament (ACL), Achilles and patellar tendons are substantially thicker and more stout than in wild-type
(WT) littermates at birth; these defects persist in adults. The affected tendon displays stronger mechanical
properties early, but becomes significantly weaker with age. No other mutants with a similar phenotype have
been described to date. Initial RNA-Seq and phenotypic analysis revealed that affected tendons in Ccn1SKO
mice acquire a gene expression profile similar to that of activated wound fibroblasts. We therefore have a
unique opportunity to identify new mechanisms regulating tendon formation and remodeling that have direct
therapeutic potential. We plan to: 1) define the function of CCN1/Cyr61 in tendon formation and maintenance
in vivo through phenotypic analysis of Ccn1SKO mice, and 2) test the hypothesis that CCN1/Cyr61 is required in
TPSCs/tenocytes to promote the tenogenic phenotype and prevent acquisition of an activated wound fibroblast
fate. Success with these studies would provide a strong rationale for future studies that evaluate the function of
CCN1/Cyr61 in tendon injury/repair and develop CCN1/Cyr61 as a therapeutic agent to promote scarless
tendon healing.
项目摘要
肌腱发育的机制是迄今为止最不了解的任何组成部分,
肌肉骨骼系统这是一个值得关注的问题,因为肌腱损伤是常见的,
有限公司愈合通常导致瘢痕组织的形成,其在组成和机械上劣于
天然肌腱,导致柔韧性降低和复发性撕裂率高。CCN家族成员
基质细胞蛋白由于其在多种纤维化病症中的关键作用而被广泛研究,但是
它们在正常纤维组织如肌腱中的作用尚不清楚。我们发现CCN 1/Cyr 61高表达,
在肌腱和韧带中,以及在肌腱/韧带祖干细胞中切除Ccn 1小鼠
使用Scx-Cre(Ccn 1 SKO)的TPSC表现出马蹄内翻足样表型。组织学分析显示,
交叉韧带(ACL)、跟腱和髌腱比野生型明显更厚、更结实
(WT)出生时同窝出生的婴儿;这些缺陷在成年人中持续存在。受影响的肌腱表现出更强的机械
性能早期,但随着年龄的增长变得明显减弱。没有其他具有类似表型的突变体
被描述到目前为止。最初的RNA-Seq和表型分析显示,Ccn 1 SKO中受影响的肌腱
小鼠获得与活化的伤口成纤维细胞相似的基因表达谱。因此,我们有一个
独特的机会,以确定新的机制,调节肌腱的形成和重塑,有直接
治疗潜力我们计划:1)确定CCN 1/Cyr 61在肌腱形成和维持中的功能
通过Ccn 1 SKO小鼠的表型分析在体内进行,和2)测试CCN 1/Cyr 61在
TPSC/肌腱细胞促进肌腱生成表型并防止获得活化的伤口成纤维细胞
命运这些研究的成功将为未来的研究提供强有力的理由,
CCN 1/Cyr 61在肌腱损伤/修复中的应用,并开发CCN 1/Cyr 61作为促进无瘢痕的治疗剂
肌腱愈合
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 }}
Karen M. Lyons其他文献
成体神経筋接合部でのCCN ファミリーの役割
CCN 家族在成人神经肌肉接头中的作用
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
大河原美静;服部高子;久保田聡;伊藤美佳子;増田章男;滝川正春;Karen M. Lyons;大野欽司 - 通讯作者:
大野欽司
Function of Ctgf in islet development and beta cell proliferation
- DOI:
10.1016/j.ydbio.2007.03.639 - 发表时间:
2007-06-01 - 期刊:
- 影响因子:
- 作者:
Michelle A. Guney;Laura Crawford;Young Ah Oh;Karen M. Lyons;Aris Economides;Maureen Gannon - 通讯作者:
Maureen Gannon
培養軟骨細胞のCCN2産生における低出力性パルス超音波(LIPUS)処置の作用メカニズムの解明
阐明低功率脉冲超声 (LIPUS) 治疗对培养软骨细胞中 CCN2 产生的作用机制
- DOI:
- 发表时间:
2017 - 期刊:
- 影响因子:0
- 作者:
西田 崇;久保田聡;青山絵理子;山中信康;Karen M. Lyons;滝川正春 - 通讯作者:
滝川正春
Karen M. Lyons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('Karen M. Lyons', 18)}}的其他基金
Title: BMP/TGFbeta crosstalk in cartilage maintenance and osteoarthritis
标题:BMP/TGFbeta 串扰在软骨维护和骨关节炎中的作用
- 批准号:
9921298 - 财政年份:2018
- 资助金额:
$ 16.94万 - 项目类别:
Title: BMP/TGFbeta crosstalk in cartilage maintenance and osteoarthritis
标题:BMP/TGFbeta 串扰在软骨维护和骨关节炎中的作用
- 批准号:
10402239 - 财政年份:2018
- 资助金额:
$ 16.94万 - 项目类别:
Title: BMP/TGFbeta crosstalk in cartilage maintenance and osteoarthritis
标题:BMP/TGFbeta 串扰在软骨维护和骨关节炎中的作用
- 批准号:
10616782 - 财政年份:2018
- 资助金额:
$ 16.94万 - 项目类别:
BMP'S IN SKELETAL GROWTH AND OSTEOGENIC DIFFERENTIATION
BMP 在骨骼生长和成骨分化中的作用
- 批准号:
8728463 - 财政年份:2013
- 资助金额:
$ 16.94万 - 项目类别:
CCN PROTEINS IN CARTILAGE FORMATION AND MAINTENANCE
CCN 蛋白在软骨形成和维护中的作用
- 批准号:
8890646 - 财政年份:2005
- 资助金额:
$ 16.94万 - 项目类别:
CCN proteins in cartilage formation and maintenance
CCN 蛋白在软骨形成和维护中的作用
- 批准号:
7460228 - 财政年份:2005
- 资助金额:
$ 16.94万 - 项目类别:
CCN proteins in cartilage formation and maintenance
CCN 蛋白在软骨形成和维护中的作用
- 批准号:
7460845 - 财政年份:2005
- 资助金额:
$ 16.94万 - 项目类别:
CCN PROTEINS IN CARTILAGE FORMATION AND MAINTENANCE
CCN 蛋白在软骨形成和维护中的作用
- 批准号:
8185896 - 财政年份:2005
- 资助金额:
$ 16.94万 - 项目类别:
CCN PROTEINS IN CARTILAGE FORMATION AND MAINTENANCE
CCN 蛋白在软骨形成和维护中的作用
- 批准号:
8296045 - 财政年份:2005
- 资助金额:
$ 16.94万 - 项目类别:
相似海外基金
Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
- 批准号:
495182 - 财政年份:2023
- 资助金额:
$ 16.94万 - 项目类别:
Investigating how alternative splicing processes affect cartilage biology from development to old age
研究选择性剪接过程如何影响从发育到老年的软骨生物学
- 批准号:
2601817 - 财政年份:2021
- 资助金额:
$ 16.94万 - 项目类别:
Studentship
RAPID: Coronavirus Risk Communication: How Age and Communication Format Affect Risk Perception and Behaviors
RAPID:冠状病毒风险沟通:年龄和沟通方式如何影响风险认知和行为
- 批准号:
2029039 - 财政年份:2020
- 资助金额:
$ 16.94万 - 项目类别:
Standard Grant
Neighborhood and Parent Variables Affect Low-Income Preschool Age Child Physical Activity
社区和家长变量影响低收入学龄前儿童的身体活动
- 批准号:
9888417 - 财政年份:2019
- 资助金额:
$ 16.94万 - 项目类别:
The affect of Age related hearing loss for cognitive function
年龄相关性听力损失对认知功能的影响
- 批准号:
17K11318 - 财政年份:2017
- 资助金额:
$ 16.94万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9320090 - 财政年份:2017
- 资助金额:
$ 16.94万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
10166936 - 财政年份:2017
- 资助金额:
$ 16.94万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9761593 - 财政年份:2017
- 资助金额:
$ 16.94万 - 项目类别:
How age dependent molecular changes in T follicular helper cells affect their function
滤泡辅助 T 细胞的年龄依赖性分子变化如何影响其功能
- 批准号:
BB/M50306X/1 - 财政年份:2014
- 资助金额:
$ 16.94万 - 项目类别:
Training Grant
Inflamm-aging: What do we know about the effect of inflammation on HIV treatment and disease as we age, and how does this affect our search for a Cure?
炎症衰老:随着年龄的增长,我们对炎症对艾滋病毒治疗和疾病的影响了解多少?这对我们寻找治愈方法有何影响?
- 批准号:
288272 - 财政年份:2013
- 资助金额:
$ 16.94万 - 项目类别:
Miscellaneous Programs














{{item.name}}会员




