SELECTIVE EXPRESSION OF FOS-RELATED AND JUN-RELATED GENES DURING OSTEOBLAST PROLIFERATION AND DIFFERENTIATION
SELECTIVE EXPRESSION OF FOS-RELATED AND JUN-RELATED GENES DURING OSTEOBLAST PROLIFERATION AND DIFFERENTIATION
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DOI：
10.1006/excr.1995.1154
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发表时间：
1995-05-01
影响因子：
3.7
通讯作者：
STEIN, G
中科院分区：
文献类型：
--
作者：
MCCABE, LR;KOCKX, M;STEIN, G
癌基因表达的发育研究和转基因动物研究暗示c-fos和其他fos和jun家族成员参与骨组织形成的调节。因此，启动实验研究的假设，即FOS和JUN相关基因的表达功能耦合到基因表达的调制，支持骨发育，我们确定了原则FOS和JUN家族成员的表达水平在两种情况下正常大鼠颅骨衍生成骨细胞的渐进分化。首先，在血清诱导的早期反应基因的表达恢复到基础水平的条件下定量细胞mRNA水平。我们的研究结果表明，高水平的c-fos，c-jun和jun B mRNA转录在成骨细胞发育的增殖期，而表达的fra-1和fra-2在分化期增强。jun D在增殖后水平仅下降30%的时间过程中组成型表达，并且fos B mRNA通过北方印迹分析检测不到。在发育序列的后期，细胞凋亡是明显的。此时，fra-1表达完全下调，而c-fos、fra-2、c-jun、jun B和jun D显示出表达的显著增强。其次，我们讨论了fos和jun家族成员的差异表达与血清反应性的关系，作为表型发育阶段的函数。增殖细胞表现出延长诱导fos和jun家族成员响应血清。而在分化细胞中，即使每2天接触新鲜血清，也对生长刺激难以抵抗，观察到fos和jun表达激增。因此，我们的数据表明，在成骨细胞分化过程中，fos和jun家族成员的基础和血清反应性存在显著差异。这些发现与将这些早期反应基因的活性与细胞生长和骨组织表型发育的调节相关联的多条证据线一致。(C)1995年学术出版社
Developmental studies of oncogene expression and transgenic animal studies implicate c-fos and other fos and jun family members in the regulation of bone tissue formation. Therefore, to initiate experimental examination of the hypothesis that expression of fos- and jun-related genes is functionally coupled to modulation of gene expression which supports bone development, we determined levels of expression of the principle fos and jun family members during progressive differentiation of normal rat calvaria-derived osteoblasts within two contexts. First, cellular mRNA levels were quantitated under conditions where expression of serum-induced early response genes had returned to basal levels. Our findings demonstrate high levels of c-fos, c-jun, and jun B mRNA transcripts during the proliferative period of osteoblast development, while expression of fra-1 and fra-2 is enhanced during the differentiation period. jun D is constitutively expressed during the time course exhibiting only a 30% decline in levels postproliferatively, and fos B mRNA is undetectable by Northern blot analyses. Late in the developmental sequence, apoptosis is evident. At this time, fra-1 expression is completely downregulated, while c-fos, fra-2, c-jun, jun B, and jun D show a dramatic enhancement in expression. Second, we addressed differential expression of fos and jun family members in relation to serum responsiveness as a function of stages of phenotypic development. Proliferating cells exhibit a prolonged induction of fos and jun family members in response to serum. While in differentiated cells, which are refractory to growth stimulus even when exposed to fresh serum every 2 days, a spike in fos and jun expression is observed. Thus, our data demonstrate significant differences in basal and serum responsiveness of fos and jun family members over the course of osteoblast differentiation. These findings are consistent with multiple lines of evidence linking activity of these early response genes to regulation of cell growth and development of the bone tissue phenotype. (C) 1995 Acndemic Press, Inc.