TRPV4, a Ca ion channel plays pivotal role in chondrogenic mechanotransduction in ATDC5

TRPV4，一种 Ca 离子通道，在 ATDC5 的软骨形成机械转导中发挥关键作用

• 批准号: 24659671
• 负责人: ISHIGURO Naoki
• 金额: $ 2.33万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659671/
• 关键词: TRPV4; SOX9; 機械的刺激; 軟骨細胞分化; ATDC5細胞; II型コラーゲン; ATDC5; プロテオグリカン; 機械受容体

It is well known that chondrocyte metabolic activity is partly regulated by physical factors.However, the specific cellular mechanosensor responsible for perception and transduction has not been fully identified in chondrocytes. It has already reported that TRPV4 activation can contribute to the process of chondrogenesis via SOX9 pathway.In this study we demonstrated that TRPV4 works as a mechanoreceptor in response to mechanical stress in chondrocytes, and to determine the intracellular mechanisms leading to the chondorogensis. Our conclusions are as follow, Mechanical stress promoted chondorogensis in ATDC5 cells with increasing mRNA expression of SOX9. Inhibition of TRPV4 by chmical and siRNA suppressed chondrogenesis effect of mechanical stress in ATDC5 cells. Ca influx by mechanical stress was suppressed by RR supplementation and TRPV4 siRNA transfection.

软骨细胞的代谢活动部分受到物理因素的调节，然而，软骨细胞中负责感知和传递的特定细胞力学传感器尚未完全确定。已有研究表明TRPV4的激活可以通过SOX 9途径参与软骨形成过程，本研究旨在阐明TRPV4作为机械力感受器参与软骨细胞对机械应力的反应，并探讨软骨形成的细胞内机制。结论：机械应力促进ATDC 5细胞软骨形成，并伴随着SOX 9 mRNA表达的增加。通过化学和siRNA抑制TRPV4抑制ATDC 5细胞中机械应力的软骨形成效应。机械应力引起的Ca内流被RR补充和TRPV4 siRNA转染抑制。

项目成果

Prognostic factors for trochanteric overgrowth after containment treatment in Legg-Calvé-Perthes disease.

Legg-Calvé-Perthes 病遏制治疗后转子过度生长的预后因素。

• DOI: 10.1097/bpb.0b013e32835f585b
• 发表时间: 2013
• 期刊: J Pediatr Orthop B
• 影响因子: 1.1
• 作者: Kitoh H;Kaneko H;Mishima K;Matsushita M;Ishiguro N
• 通讯作者: Ishiguro N

MPFL再建＋脛骨粗面移行術後の膝蓋骨高に関するX線学的検討ー治療成績評価における各種計測法の違いー

MPFL重建+胫骨粗隆过渡后髌骨高度X线检查 - 各种测量方法评估治疗效果的差异 -

• 发表时间: 2012
• 期刊: JOSKAS
• 作者: 酒井忠博;平岩秀樹;濱田恭;山本隆一郎;大間知孝顕;松川哲也;大野洋平;中島基成;石塚真哉;石黒直樹
• 通讯作者: 石黒直樹

A Novel SOX9 H169Q Mutation in a Family With Overlapping Phenotype of Mild Campomelic Dysplasia and Small Patella Syndrome

• DOI: 10.1002/ajmg.a.36134
• 发表时间: 2013-10-01
• 期刊: AMERICAN JOURNAL OF MEDICAL GENETICS PART A
• 影响因子: 2
• 作者: Matsushita, Masaki;Kitoh, Hiroshi;Nishimura, Gen
• 通讯作者: Nishimura, Gen

Novel compound heterozygous mutations in the cathepsin K gene in Japanese female siblings with pyknodysostosis

患有致密性骨性骨质疏松症的日本女性同胞中组织蛋白酶 K 基因的新型复合杂合突变

• DOI: 10.1159/000336581
• 发表时间: 2012
• 期刊: Mol Syndromol
• 影响因子: 1.1
• 作者: Matsushita M;Kitoh H;Kaneko H;Mishima K;Itoh Y;Hattori T;Ishiguro N
• 通讯作者: Ishiguro N

Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: an open-labeled clinical trial.

perhexiline在治疗纤维肿瘤的骨质体progressecriva：一项开放标记的临床试验中。

• DOI: 10.1186/1750-1172-8-163
• 发表时间: 2013-10-16
• 期刊: Orphanet journal of rare diseases
• 影响因子: 3.7
• 作者: Kitoh H;Achiwa M;Kaneko H;Mishima K;Matsushita M;Kadono I;Horowitz JD;Sallustio BC;Ohno K;Ishiguro N
• 通讯作者: Ishiguro N