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

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.
项目总结

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)

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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

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{{ 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:
2011 Cartilage Biology & Pathology GRC
2011年软骨生物学
  • 批准号:
    8119807
  • 财政年份:
    2011
  • 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:

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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。
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