Function of fos family genes in the differentiation of chicken chondrocytes

在本研究中，我们分析了Fos/Jun家族蛋白（AP-1）的表达水平以及各Fos/Jun家族基因异位表达在培养的鸡早期胚胎软骨细胞或肢芽中的生物学效应。我们建立了一种通过微注射禽复制能力逆转录病毒载体在鸡胚（1.5天）全肢区引入和表达外源基因的方法。所有已知的鸡fos或jun家族基因（c-fos、fra-2、c-jun或junD）在肢芽中的异位表达对骨的模式形成和形态没有影响。然而，当引入FBJ-MuSV的v-fos基因时，胫骨、腓骨和股骨等所有长骨均明显缩短（为未感染对照的40-70%）。病理分析表明，v-fos病毒感染的软骨细胞呈现增殖型软骨细胞形态，向成熟或增生性软骨细胞分化受到明显抑制。我们分析了Fos或Jun家族蛋白在体外培养的来自胸骨下部和上部区域的软骨细胞（分别为LS和US）中的表达水平。两种软骨细胞最明显的差异是c-Jun的表达水平，LS越不成熟，c-Jun的表达水平越高。c-Jun在US细胞中的异位表达可刺激细胞生长，抑制细胞分化，提示c-Jun功能在软骨细胞分化中的重要作用。

In this study, we have analyzed the expression levels of Fos/Jun family proteins (AP-1) and the biological effects of ectopic expression of each fos/jun family genes in the cultured chondrocytes or in limb buds of early chicken embryo.1.We have established a methodology to introduce and express exogenous genes in the entire limb region of chicken embryo (day 1.5) by microinjecting avian replication-competent retrovirus vectors. The ectopic expression of all the known fos or jun family genes of chicken (c-fos, fra-2, c-jun or junD) in the limb buds caused no changes in the pattern formation of bones or in the morphology. When the v-fos gene of FBJ-MuSV was introduced, however, all the long bones such as tibia, fibula and femur were shortened significantly (40-70% of the uninfected counterpart). Pathological analysis indicated that v-fos virus infected chondrocytes have assumed the morphology of proliferating chondrocytes and the differentiation into mature or hypertropic chondrocytes were drastically inhibited.2.We have analyzed the expression levels of Fos or Jun family proteins in the cultured chondrocytes deribed from both lower and upper region of steruna (LS and US,respectively). The most clear difference observed between the two types of chondrocytes were the expression levels in c-Jun, LS,which is in more immature stage, expresses higher levels of c-Jun. And ectopic expression of c-Jun in US cells caused stimulation of cellular growth and inhibition of differentiation, indicating the importance of c-Jun function in the chondrocyte differentiation.