Function of fos family genes in the differentiation of chicken chondrocytes

本研究分析了Fos/Jun家族蛋白（AP-1）在培养的早期鸡胚软骨细胞和肢芽中的表达水平，以及Fos/Jun家族各基因异位表达的生物学效应。1.建立了鸡胚（1.5d）肢区全基因导入和表达的方法。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不会引起骨骼图案形成或形态学的变化。然而，当引入FBJ-MuSV的v-fos基因时，所有长骨如胫骨、腓骨和股骨都显著缩短（未感染对应物的40-70%）。病理学分析表明，v-fos病毒感染的软骨细胞已呈现增殖软骨细胞的形态，向成熟或肥大软骨细胞的分化受到明显抑制。2.我们分析了培养的软骨细胞中Fos和Jun家族蛋白的表达水平。两种软骨细胞之间最明显的差异是c-Jun的表达水平，LS在更不成熟的阶段表达更高水平的c-Jun，而c-Jun在US细胞中的异位表达导致细胞生长刺激和分化抑制，表明c-Jun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.