PDF(Pubmed)
Abstract：
OBJECTIVE: Homeobox genes of the Hox class are required for proper patterning of skeletal elements and play a role in cartilage differentiation. In transgenic mice with overexpression of Hoxc8 and Hoxd4 during cartilage development, the authors observed severe defects, namely, physical instability of cartilage, accumulation of immature chondrocytes, and decreased maturation to hypertrophy. To define the molecular basis underlying these defects, the authors performed gene expression profiling using the Affymetrix microarray platform.
RESULTS: Primary chondrocytes were isolated from Hoxc8- and Hoxd4-transgenic mouse embryo rib cartilage at 18.5 days of gestation. In both cases, differentially expressed genes were identified that have a role in cell proliferation and cell cycle regulation. A comparison between the controls for both experimental groups did not reveal significant differences, as expected. However, the repertoires of differentially expressed genes were found not to overlap between Hoxc8- and Hoxd4-transgenic cartilage. This included different Wnt genes, cell cycle, and apoptosis regulators.
CONCLUSIONS: Overexpression of Hoxc8 and Hoxd4 transcription factors alters transcriptional profiles in chondrocytes at E18.5. The differences in repertoires of altered gene expression between the 2 transgenic conditions suggest that the molecular mechanisms underlying the cartilage defects may be different in both transgenic paradigms, despite apparently similar phenotypes.
RESULTS: Primary chondrocytes were isolated from Hoxc8- and Hoxd4-transgenic mouse embryo rib cartilage at 18.5 days of gestation. In both cases, differentially expressed genes were identified that have a role in cell proliferation and cell cycle regulation. A comparison between the controls for both experimental groups did not reveal significant differences, as expected. However, the repertoires of differentially expressed genes were found not to overlap between Hoxc8- and Hoxd4-transgenic cartilage. This included different Wnt genes, cell cycle, and apoptosis regulators.
CONCLUSIONS: Overexpression of Hoxc8 and Hoxd4 transcription factors alters transcriptional profiles in chondrocytes at E18.5. The differences in repertoires of altered gene expression between the 2 transgenic conditions suggest that the molecular mechanisms underlying the cartilage defects may be different in both transgenic paradigms, despite apparently similar phenotypes.
摘要：
目的：Hox类的Homeobox基因是骨骼元素的正确模式所必需的，并且在软骨分化中起作用。在软骨发育过程中过表达Hoxc8和Hoxd4的转基因小鼠中，作者观察到严重的缺陷，即,软骨的物理不稳定性，未成熟软骨细胞的积累，和减少成熟到肥大。为了定义这些缺陷背后的分子基础，作者使用Affymetrix微阵列平台进行了基因表达谱分析.
结果：在妊娠18.5天从Hoxc8和Hoxd4转基因小鼠胚胎肋软骨中分离出原代软骨细胞。在这两种情况下，差异表达的基因被鉴定为在细胞增殖和细胞周期调节中起作用。两个实验组的对照之间的比较没有发现显着差异，如预期。然而,差异表达基因库在Hoxc8-和Hoxd4-转基因软骨之间没有重叠。这包括不同的Wnt基因，细胞周期,和凋亡调节剂。
结论：在E18.5时，Hoxc8和Hoxd4转录因子的过表达改变了软骨细胞的转录谱。两种转基因条件之间改变的基因表达库的差异表明，两种转基因范式中软骨缺损的分子机制可能不同。尽管表型相似。
结果：在妊娠18.5天从Hoxc8和Hoxd4转基因小鼠胚胎肋软骨中分离出原代软骨细胞。在这两种情况下，差异表达的基因被鉴定为在细胞增殖和细胞周期调节中起作用。两个实验组的对照之间的比较没有发现显着差异，如预期。然而,差异表达基因库在Hoxc8-和Hoxd4-转基因软骨之间没有重叠。这包括不同的Wnt基因，细胞周期,和凋亡调节剂。
结论：在E18.5时，Hoxc8和Hoxd4转录因子的过表达改变了软骨细胞的转录谱。两种转基因条件之间改变的基因表达库的差异表明，两种转基因范式中软骨缺损的分子机制可能不同。尽管表型相似。
