Chondrocyte hypertrophy and apoptosis induced by GROalpha require three-dimensional interaction with the extracellular matrix and a co-receptor role of chondroitin sulfate and are associated with the mitochondrial splicing variant of cathepsin B.

Olivotto E; Vitellozzi R; Fernandez PFalcieri EBattistelli MBurattini SFacchini AFlamigni FSanti SFacchini ABorzi RM

首页> 外文期刊>Journal of Cellular Physiology >Chondrocyte hypertrophy and apoptosis induced by GROalpha require three-dimensional interaction with the extracellular matrix and a co-receptor role of chondroitin sulfate and are associated with the mitochondrial splicing variant of cathepsin B.

【24h】

Chondrocyte hypertrophy and apoptosis induced by GROalpha require three-dimensional interaction with the extracellular matrix and a co-receptor role of chondroitin sulfate and are associated with the mitochondrial splicing variant of cathepsin B.

机译：软骨细胞肥大和凋亡诱导GROalpha需要三维交互细胞外基质和受体硫酸软骨素和相关联的角色与线粒体的剪接变体组织蛋白酶B。

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

CXCR2 ligands contribute to chondrocyte hypertrophy and apoptosis, important determinants in cartilage pathophysiology. We unraveled the kinetics of signaling, biochemical, transcriptional, and morphological events triggered by GROalpha in human osteoarthritic chondrocytes kept in three-dimensional culture. p38 MAPK activation was assessed with a highly sensitive ELISA. Effector caspase activation was evaluated by cleavage of a fluorogenic substrate. Gene expression of key markers of hypertrophy (MMP-13, Runx-2) and matrix synthesis (aggrecan), and of cathepsin B isoform CB(-2,3) was evaluated by real time PCR. Occurrence of the morphological markers of apoptosis was investigated by transmission electron microscopy (TEM). GROalpha led to p38 MAPK activation in passaged chondrocytes cultured in micromass but not as a high-density monolayer. This caused the downstream triggering of chondrocyte hypertrophy (MMP-13 and Runx-2 upregulation, and calcium deposition) and apoptosis/anoikis following concurrenceof matrix degrading activity, and inhibition of matrix synthesis which also involved the induction of CB(-2,3). These phenomena proved to be dependent on the co-receptor role of sulfated glycosaminoglycans (sGAG) and the activation of p38 MAPK, since they were abrogated either by preincubation with soluble chondroitin-4 sulfate or p38 MAPK inhibitors. The co-receptor role of sGAG was further demonstrated by colocalization experiments of these molecules with GROalpha in the stimulated micromasses. These findings suggest that extracellular matrix exerts a regulatory role in chondrocytes differentiation, and that meaningful investigation of the effects of chemokines on chondrocyte biology requires culture conditions respectful of both the differentiated status of the chondrocytes and of their three-dimensional interaction with the extracellular matrix.

机译：CXCR2配体促进软骨细胞肥大和凋亡,重要的决定因素在软骨病理生理学。信号动力学、生化、转录和形态事件人类骨关节炎的GROalpha引发的软骨细胞在三维文化。p38 MAPK激活与高度评价敏感的ELISA。评估fluorogenic衬底的乳沟。基因表达的肥大的主要标记(MMP-13 Runx-2)和矩阵合成(aggrecan),和组织蛋白酶B同种型CB(2、3)评估实时PCR。标记细胞凋亡研究的透射电子显微镜(TEM)。导致p38 MAPK在通道激活软骨细胞培养在micromass但不作为高密度单层。下游引发的软骨细胞肥大(MMP-13和Runx-2 upregulation和钙沉积)和细胞凋亡/女性concurrenceof矩阵退化活动,抑制矩阵合成也涉及的感应CB(2、3)。被证明是依赖现象受体的作用硫酸粘多糖(sGAG)和p38 MAPK的激活,因为他们废除通过预孵化了可溶性硫酸chondroitin-4或p38 MAPK抑制剂。进一步证明了colocalization这些分子与GROalpha实验micromasses刺激。表明,细胞外基质产生在软骨细胞分化的监管作用,和有意义的调查的效果趋化因子对软骨细胞生物学需要文化环境的尊重软骨细胞和分化状态三维交互细胞外基质。

著录项

来源
《Journal of Cellular Physiology》 |2007年第2期|417-427|共11页
作者
Olivotto E; Vitellozzi R; Fernandez PFalcieri EBattistelli MBurattini SFacchini AFlamigni FSanti SFacchini ABorzi RM;
展开▼
作者单位

Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna, Italy.;

展开▼
收录信息
原文格式 PDF
正文语种英语
中图分类细胞生物学;
关键词
Chondrocyte; Hypertrophy; Cathepsin BChemokinesExtracellular MatrixChondroitin SulfatesMitogen-Activated Protein KinasesMitogen-Activated Protein Kinase p38Apoptosis;

机译：Chondrocyte;Hypertrophy CathepsinSulfatesMitogen-Activated蛋白质KinasesMitogen-Activated蛋白激酶p38Apoptosis;

Chondrocyte hypertrophy and apoptosis induced by GROalpha require three-dimensional interaction with the extracellular matrix and a co-receptor role of chondroitin sulfate and are associated with the mitochondrial splicing variant of cathepsin B.

摘要

著录项

相关主题

期刊订阅