Project description:This SuperSeries is composed of the following subset Series: GSE18991: Overexpression of Hoxd4 transcription factor alters transcriptional profiles in mouse chondrocytes at E18.5 GSE18992: Overexpression of Hoxc8 transcription factor alters transcriptional profiles in mouse chondrocytes at E18.5!Series_overall_design = Refer to individual Series Refer to individual Series
Project description:ObjectiveHomeobox 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.ResultsPrimary 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.ConclusionOverexpression 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.
Project description: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 during cartilage development, we 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, we performed gene expression profiling using the Affymetrix microarray platform.
Project description: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 during cartilage development, we 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, we performed gene expression profiling using the Affymetrix microarray platform. Embryos were dissected from four different mouse litters at E18.5. Embryos from each litter were grouped according their genotype: TA=control; TR=transgenic.
Project description:Timps are natural metalloproteinase inhibitors that direct the cell microenvironment in health and disease, yet the essential requirement of this gene family in mammals is unknown. We generated quadruple Timp deficient mice lacking Timp1, Timp2, Timp3 and Timp4 (TIMPless) and found that Timp function is essential for postnatal lifespan, lung form and function and skeletogenesis. TIMPless mice survive embryogenesis but develop pervasive skeletal aberrations characterized by axial cartilage overgrowth and growth plate closure in long bones. We performed microarray analysis to identify signaling pathways affected by the loss of the entire Timp family in sternal cartilage.
Project description:Timps are natural metalloproteinase inhibitors that direct the cell microenvironment in health and disease, yet the essential requirement of this gene family in mammals is unknown. We generated quadruple Timp deficient mice lacking Timp1, Timp2, Timp3 and Timp4 (TIMPless) and found that Timp function is essential for postnatal lifespan, lung form and function and skeletogenesis. TIMPless mice survive embryogenesis but develop pervasive skeletal aberrations characterized by axial cartilage overgrowth and growth plate closure in long bones. We performed microarray analysis to identify signaling pathways affected by the loss of the entire Timp family in sternal cartilage. Cartilage, excluding the xiphoid process, was macrodissected from the sternums of 4-week old WT and TIMPless mice (n=6/genotype).
Project description:RATIONALE: Shark cartilage extract may help shrink or slow the growth of colorectal cancer or breast cancer cells.
PURPOSE: Randomized phase III trial to determine the effectiveness of shark cartilage in treating patients who have advanced colorectal cancer or advanced breast cancer.
Project description:Microarray-data (Illumina MouseWG-6 v2) of knee cartilage of wild-type and Dio2 -/- -mice were re-analyzed to identify differential expressed genes independent of mechanical loading conditions by forced treadmill-running. Differential expression analyses of articular cartilage of Dio2-/- (N = 9) and wild-type-mice (N = 11) while applying a cutoff threshold (P < 0.05 (FDR) and FC > |1,5|) resulted in 1 probe located in Calreticulin (Calr) that was found significantly downregulated in Dio2-/- mice. The beneficial homeostatic state of articular cartilage in Dio2-/- mice is accompanied with significant lower expression of Calr. Functional analyses further showed that upregulation of Calr expression could act as an initiator of cartilage destruction.