Esophageal cancer related gene 4 (ECRG4) is a marker of articular chondrocyte differentiation and cartilage destruction
Esophageal cancer related gene 4 (ECRG4) is a marker of articular chondrocyte differentiation and cartilage destruction
复制标题
DOI：
10.1016/j.gene.2009.08.015
复制
发表时间：
2009-12-01
期刊：
影响因子：
3.5
通讯作者：
Chun, Jang-Soo
中科院分区：
文献类型：
--
作者：
Huh, Yun Hyun;Ryu, Je-Hwang;Chun, Jang-Soo
为了鉴定调控软骨发育和退化的新基因，我们筛选了软骨特异性表达序列标签数据库。根据软骨细胞特异性和未知功能的标准，选择食管癌相关基因4（ECRG 4）。与各种其他小鼠组织相比，ECRG 4表达在软骨细胞和软骨中特别丰富。ECRG 4是一种分泌蛋白，在分泌后进行切割。该蛋白质以依赖于分化状态的方式在软骨细胞中特异性表达。在间充质细胞中的表达非常低，并且在软骨形成分化期间显著增加。在体外和体内，分化的软骨细胞中的ECRG 4水平在肥大成熟过程中降低，另外在由白细胞介素-1 β或连续传代培养诱导的去分化软骨细胞、人骨关节炎软骨和实验小鼠骨关节炎软骨的软骨细胞中也降低。然而，在原代培养细胞系统中的异位表达或外源ECRG 4处理不影响间充质细胞的软骨形成、软骨细胞的肥大成熟或分化的软骨细胞的去分化。此外，在软骨组织中过度表达ECRG 4的转基因小鼠中，软骨发育和细胞外基质的组织不受影响。然而，ECRG 4的异位表达降低了原代培养软骨细胞的增殖。虽然ECRG 4表达的潜在机制和具体作用仍有待更详细地阐明，但我们的结果支持其作为分化的关节软骨细胞和软骨破坏的标志物的功能。(C)2009 Elsevier B. V.保留所有权利。
With the aim of identifying novel genes regulating cartilage development and degeneration, we screened a cartilage-specific expressed sequence tag database. Esophageal cancer related gene 4 (ECRG4) was selected, based on the criteria of chondrocyte-specific' and 'unknown function.' ECRG4 expression was particularly abundant in chondrocytes and cartilage, compared to various other mouse tissues. ECRG4 is a secreted protein that undergoes cleavage after secretion. The protein is specifically expressed in chondrocytes in a manner dependent on differentiation status. The expression is very low in mesenchymal cells, and dramatically increased during chondrogenic differentiation. The ECRG4 level in differentiated chondrocytes is decreased during hypertrophic maturation, both in vitro and in vivo, and additionally in dedifferentiating chondrocytes induced by interleukin-1 beta or serial subculture, chondrocytes of human osteoarthritic cartilage and experimental mouse osteoarthritic cartilage. However, ectopic expression or exogenous ECRG4 treatment in a primary culture cell system does not affect chondrogenesis of mesenchymal cells, hypertrophic maturation of chondrocytes or dedifferentiation of differentiated chondrocytes. Additionally, cartilage development and organization of extracellular matrix are not affected in transgenic mice overexpressing ECRG4 in cartilage tissue. However, ectopic expression of ECRG4 reduced proliferation of primary culture chondrocytes. While the underlying mechanisms of ECRG4 expression and specific roles remain to be elucidated in more detail, our results support its function as a marker of differentiated articular chondrocytes and cartilage destruction. (C) 2009 Elsevier B.V. All rights reserved.