Identification and characterization of a unique chondrocyte gene involved in transition to hypertrophy.

Identification and characterization of a unique chondrocyte gene involved in transition to hypertrophy.
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鉴定和表征参与向肥大转变的独特软骨细胞基因。

DOI:
10.1006/excr.1996.0219
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发表时间:
1996
期刊:
Experimental cell research.
影响因子:
--
通讯作者:
Reynolds,PR
Reynolds,PR
中科院分区:
--
文献类型:
--
作者:
Reynolds,SD;Johnston,C;Leboy,PS;O'Keefe,RJ;Puzas,JE;Rosier,RN;Reynolds,PR

文献摘要

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在生长的长骨中分化软骨细胞的特征已经通过有限数量的基因的表达改变来定义。为了扩大这一套,我们已经应用差异显示,以确定基因表达的矿化或非矿化软骨细胞。Band 17基因具有以下特点:(1)Band 17基因主要在软骨中表达,而在关节软骨中未检测到,在其他组织中检测不到或表达较弱。(2)带17的表达在空间上局限于长骨和胚胎椎骨生长板中软骨细胞的下增殖/上肥大区。(3)通过抗坏血酸盐处理诱导胸骨软骨祖细胞肥大表型增加Band 17的表达。(4)短期单层培养中生长板软骨细胞肥大的诱导与Band 17信使的快速但短暂的升高相关。我们对这些发现的解释是,带17的表达与向肥大的转变有关,而与肥大表型的维持无关。对带17基因3′端cDNA序列和基因组结构的分子分析表明,带17是一个单拷贝基因,转录成四个信使。预测这些信息的选择性剪接会导致两种蛋白质在C末端有131个氨基酸的差异。较长的蛋白质含有C-末端共有序列,其潜在地将该蛋白质靶向内质网的内腔。在人类中存在一个带17同源物,提示带17功能在哺乳动物中具有保守性。总之,表达模式和预测的一级结构将Band 17鉴定为所有先前已知的软骨细胞基因中唯一的。
The character of differentiating chondrocytes in growing long bones has been defined by altered expression of a limited number of genes. To expand this set we have applied differential display to identify genes expressed in either mineralizing or nonmineralizing chondrocytes. One such gene,Band 17,has the following characteristics: (1)Band 17expression is predominantly found in cartilage destined for mineralization.Band 17mRNA is undetectable in articular cartilage and undetectable or weak in all other tissues tested. (2)Band 17expression is spatially restricted to the lower proliferative/upper hypertrophic zone of chondrocytes in the growth plate of long bones and embryonic vertebrae. (3) Induction of a hypertrophic phenotype in progenitor sternal chondrocytes by treatment with ascorbate increases expression ofBand 17.(4) Induction of hypertrophy in growth plate chondrocytes in short-term monolayer cultures correlates with a rapid but transient rise inBand 17message. Our interpretation of these findings is thatBand 17expression is associated with the transition to hypertrophy, not maintenance of the hypertrophic phenotype. Molecular analysis of the 3′ end ofBand 17cDNAs and genomic structure has shown thatBand 17is a single copy gene transcribed into four messages. Alternative splicing of these messages is predicted to result in two proteins that differ at the C-terminal by 131 amino acids. The longer protein contains a C-terminal consensus sequence that potentially targets this protein to the lumen of the endoplasmic reticulum. There is aBand 17homologue in humans, suggesting conservation ofBand 17function in mammals. In summary, the pattern of expression and the predicted primary structure identifyBand 17as unique among all previously known chondrocyte genes.