Analysis of BMP-mediated cartilage formation anddifferentiation, and cartilage repair

BMP介导的软骨形成和分化以及软骨修复分析

• 批准号: 21390421
• 负责人: TSUMAKI Noriyuki
• 金额: $ 10.07万
• 依托单位: Kyoto University (2011-2012)Osaka University (2009-2010)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390421/
• 关键词: 軟骨細胞; 内軟骨性骨化; ノックアウトマウス; 細胞分化; HDAC4; 軟骨; 転写制御; トランスジェニックマウス; コラーゲン

Sox9 in mesenchymal progenitors is important for their differentiation intochondrocytes, but its functions after differentiation into chondrocytes have not beendetermined. To investigate Sox9 function in chondrocytes precisely, we deleted Sox9genes after differentiation into chondrocytes in mice. Sox9 inactivation inchondrocytes resulted in apoptosis. Molecular analysis revealed that Sox9 sustainswhich are involved in chondrocyte differentiation, we discovered that chondrocytehypertrophy was markedly delayed in the growth plate cartilage in mice lacking saltinducible kinase 3 (SIK3). SIK3 was required for anchoring HDAC4 in the cytoplasm,thereby releasing MEF2C, a critical facilitator of chondrocyte hypertrophy, fromsuppression by HDAC4 in the nuclei. From these results, we concluded that SIK3facilitates chondrocyte hypertrophy during formation and maintenance of cartilage

Sox 9在骨髓间充质祖细胞向软骨细胞分化过程中起重要作用，但其在软骨细胞分化后的功能尚未明确。为了更精确地研究Sox 9在软骨细胞中的功能，我们在小鼠分化为软骨细胞后删除了Sox 9基因。Sox 9失活导致软骨细胞凋亡。分子分析显示Sox 9维持参与软骨细胞分化，我们发现缺乏盐诱导激酶3（SIK3）的小鼠生长板软骨中软骨细胞肥大明显延迟。需要SIK3将HDAC4锚定在细胞质中，从而释放MEF2C，软骨细胞肥大的关键促进剂，使其免受HDAC4在细胞核中的抑制。从这些结果中，我们得出结论，在软骨形成和维持过程中，SIK3促进软骨细胞肥大

项目成果

Essential mesenchymal role of small GTPase Rac1 in interdigital programmed cell death during limb development

• DOI: 10.1016/j.ydbio.2009.09.014
• 发表时间: 2009-11-15
• 期刊: DEVELOPMENTAL BIOLOGY
• 影响因子: 2.7
• 作者: Suzuki, Dai;Yamada, Atsushi;Kamijo, Ryutaro
• 通讯作者: Kamijo, Ryutaro

内軟骨性骨化におけるCyp261の役割の解析

Cyp261在软骨内骨化中的作用分析

• 发表时间: 2011
• 作者: 峯岸芳樹;坂井靖夫;細川亙;吉川秀樹;妻木範行
• 通讯作者: 妻木範行

Regulatory sequences ofthe a2(XI) collgen chain gene andchondrogenesis

a2(XI)胶原链基因的调控序列与软骨形成

• 发表时间: 2009
• 作者: Izawa T;Okazaki K;Tashiro Y;Matsubara H;Miura H;Matsuda S;Hashizume M;Iwamoto Y;妻木範行
• 通讯作者: 妻木範行

皮膚細胞からの軟骨細胞誘導

从皮肤细胞诱导软骨细胞

• 发表时间: 2011
• 作者: 平松久仁彦;笹川覚;玉山英達;中川加奈子;吉川秀樹;妻木範行
• 通讯作者: 妻木範行

Regulatory sequences of the a2 (XI) collgen chain gene and chondrogenesis

a2 (XI) 胶原链基因的调控序列和软骨形成

• 发表时间: 2009
• 作者: Nishimura T;Umeki A;Takewa Y;Ando M;Mizuno T;Tsukiya T;Yamazaki K;Ono M;Kyo S;Taenaka Y;Tatsumi E.;妻木範行
• 通讯作者: 妻木範行