Comprehensive analysis of the inducer that degrades the extracellular matrix of articular cartilage

降解关节软骨细胞外基质的诱导剂综合分析

• 批准号: 24659663
• 负责人: INUI Hiroshi
• 金额: $ 2.41万
• 依托单位: The University of Tokyo
• 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-24659663/
• 关键词: 関節病学

We identified transcription factor that induce ADAMTS5, a crucial proteinase for osteoarthritis development by promotor analysis. The endogenous Adamts5 expression in primary chondrocyte derived from knockout mouse of this gene was decreased. In the ex vivo culture of femoral head cartilage from mesenchymal cell-specific knockout of this gene, aggrecanolysis was significantly lower than that in the control cartilage. Finally, we performed the experimental mouse osteoarthritis model in conditional knockout mouse, the conditional knockout of this gene resulted in the acceleration of osteoarthritis development because of the up-regulation of chondrocyte apoptosis. We will investigate moderate suppression of this gene could suppress the osteoarthritis development by using inhibitor of signals related to this gene.

我们通过启动子分析确定了诱导ADAMTS5的转录因子，ADAMTS5是骨关节炎发展的关键蛋白酶。该基因敲除小鼠的原代软骨细胞内源性Adamts 5表达降低。在离体培养的股骨头软骨从间充质细胞特异性敲除该基因，aggrecanolysis显着低于对照软骨。最后，我们在条件性基因敲除小鼠中建立了实验性小鼠骨关节炎模型，该基因的条件性敲除由于软骨细胞凋亡的上调而导致骨关节炎发展的加速。我们将通过使用与该基因相关的信号抑制剂来研究适度抑制该基因可以抑制骨关节炎的发展。

项目成果

NF-κBファミリーメンバーRelA/p65は、軟骨細胞のアポトーシスを阻害することで、骨格形成と変形性関節症の進行を制御する.

NF-κB 家族成员 RelA/p65 通过抑制软骨细胞凋亡来调节骨骼形成和骨关节炎进展。

• 作者: 小林寛;平田真;伊藤祥三;斎藤琢;鄭雄一;中村耕三;川口浩
• 通讯作者: 川口浩

Identification of Fibroblast Growth Factor-18 as a Molecule to Protect Adult Articular Cartilage by Gene Expression Profiling*

• DOI: 10.1074/jbc.m113.524090
• 发表时间: 2014-04-04
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Mori, Yoshifumi;Saito, Taku;Kawaguchi, Hiroshi
• 通讯作者: Kawaguchi, Hiroshi

NF-κB family member Rela/p65 in chondrocytes controls skeletal growth and osteoarthritis development by inhibiting chondrocyte apoptosis.

软骨细胞中的 NF-κB 家族成员 Rela/p65 通过抑制软骨细胞凋亡来控制骨骼生长和骨关节炎的发展。

• 作者: Kobayashi H, Hirata M, Saito T, Itoh S, ;Hosaka Y;Akiyama H;Chung UI, Kawaguchi H.
• 通讯作者: Chung UI, Kawaguchi H.

Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development

• DOI: 10.1073/pnas.1207458110
• 发表时间: 2013-01-29
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Hosaka, Yoko;Saito, Taku;Kawaguchi, Hiroshi
• 通讯作者: Kawaguchi, Hiroshi