Clarification of signal transmission mechanism in mesenchymal cells during spontaneous cartilage regeneration induced by multi-functional synthetic gel

多功能合成凝胶诱导自发软骨再生过程中间充质细胞信号传递机制的阐明

• 批准号: 23240070
• 负责人: YASUDA Kazunori
• 金额: $ 31.28万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23240070/
• 关键词: ダブルネットワークゲル; 軟骨分化; 自然再生; 細胞内情報伝達; 光イメージング; 細胞メカニクス; 質量分析; 軟骨分子

This study discovered several important phenomena and their molecular mechanisms during chondrogenic differentiation and regeneration of mesenchymal cells induced by the PAMPS/PDMAAm gel or soluble proteins:(1) ATP oscillation, which depends on oscillation of both the mitochondrial respiration and the glycolysis, was induced by calcium ion oscillation. The ATP oscillation does not control cell differentiation but controls cell aggregation and tissue formation via controlling secretion of soluble proteins. (2) Young's modulus of a chondrogenic precursor cell increased to a significantly greater degree during differentiation induced by the gel than during differentiation induced by Insulin. (3) Both the BMP-Smad signaling pathway and the IGF-depending signaling pathway were specifically activated during the differentiation induced by DN gel in comparison with that induced by Insulin. (4) The proteomics analysis showed that the gel has a function as a reservoir of soluble factors.

本研究发现PAMPS/PDMAAm凝胶或可溶性蛋白诱导间充质细胞成软骨分化和再生过程中的几个重要现象及其分子机制：(1)钙离子振荡诱导ATP振荡，ATP振荡依赖于线粒体呼吸和糖酵解的振荡。ATP振荡不控制细胞分化，但通过控制可溶性蛋白的分泌来控制细胞聚集和组织形成。(2)凝胶诱导软骨前体细胞分化过程中杨氏模量的增加程度明显大于胰岛素诱导的分化过程。(3)与胰岛素诱导的分化相比，DN凝胶诱导的BMP-Smad信号通路和依赖igf的信号通路均被特异性激活。(4)蛋白质组学分析表明，该凝胶具有可溶性因子储存库的功能。

项目成果

Proteoglycans and Glycosaminoglycans Improve Toughness of Biocompatible Double Network Hydrogels

• DOI: 10.1002/adma.201303387
• 发表时间: 2014
• 期刊: Advanced Materials
• 影响因子: 29.4
• 作者: Yu Zhao;Tasuku Nakajima;Jing Jing Yang-Jing;T. Kurokawa;J. Liu;Jishun Lu;Shuji Mizumoto;K. Sugahara-

人工軟骨のIn vitro摩擦摩耗特性評価

人工软骨体外摩擦磨损特性评价

• 发表时间: 2012
• 作者: 田中 佑治;長橋史弥
• 通讯作者: 長橋史弥

Gene expression profile of the cartilage tissue spontaneously regenerated in vivo by using a novel double-network gel: comparisons with the normal articular cartilage.

• DOI: 10.1186/1471-2474-12-213
• 发表时间: 2011-09-29
• 期刊: BMC musculoskeletal disorders
• 影响因子: 2.3
• 作者: Imabuchi R;Ohmiya Y;Kwon HJ;Onodera S;Kitamura N;Kurokawa T;Gong JP;Yasuda K
• 通讯作者: Yasuda K

Spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect created in the femoral condyle using a novel double-network hydrogel.

• DOI: 10.1186/1471-2474-12-49
• 发表时间: 2011-02-22
• 期刊: BMC musculoskeletal disorders
• 影响因子: 2.3
• 作者: Yokota M;Yasuda K;Kitamura N;Arakaki K;Onodera S;Kurokawa T;Gong JP
• 通讯作者: Gong JP

Implantation of autogenous meniscal fragments wrapped with a fascia sheath enhances fibrocartilage regeneration in vivo in a large harvest site defect. An experimental study with sheep.

用筋膜鞘包裹的自体半月板碎片的植入可增强大面积收获部位缺损的体内纤维软骨再生。

• 发表时间: 2013
• 作者: Kawaguchi Y;Kondo E;Kitamura N;Kobayashi Y;Kimura M;Yunoki S;Yasuda K
• 通讯作者: Yasuda K