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Rattus norvegicus
15 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
OBJECTIVE: To analyze genome-wide changes in chondrocyte gene expression in a surgically induced model of early osteoarthritis (OA) in rats, to assess the similarity of this model to human OA, and to identify genes and mechanisms leading to OA pathogenesis. METHODS: OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham-operated knees. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression. Expression patterns of selected dysregulated genes, including Col2a1, Mmp13, Adamts5, Ctsc, Ptges, and Cxcr4, were validated by real-time polymerase chain reaction, immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery. RESULTS: After normalization, comparison of OA and sham-operated samples showed 1,619 differentially expressed probe sets with changes in their levels of expression >/=1.5-fold, 722 with changes >/=2-fold, 135 with changes >/=4-fold, and 20 with changes of 8-fold. Dysregulated genes known to be involved in human OA included Mmp13, Adamts5, and Ptgs2, among others. Several dysregulated genes (e.g., Reln, Phex, and Ltbp2) had been identified in our earlier microarray study of hypertrophic chondrocyte differentiation. Other genes involved in cytokine and chemokine signaling, including Cxcr4 and Ccl2, were identified. Changes in gene expression were also observed in the contralateral knee, validating the sham operation as the appropriate control. CONCLUSION: Our results demonstrate that the animal model mimics gene expression changes seen in human OA, supporting the relevance of newly identified genes and pathways to early human OA. We propose new avenues for OA pathogenesis research and potential targets for novel OA treatments, including cathepsins and cytokine, chemokine, and growth factor signaling pathways, in addition to factors controlling the progression of chondrocyte differentiation.
Publication Title
Global analyses of gene expression in early experimental osteoarthritis.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Cartilage destruction in osteoarthritis (OA) results from disturbed chondrocyte metabolism. Here, we used microarrays to show that TGF alpha and CCL2 are simultaneously upregulated in a rat model of OA and cooperate to drive cartilage degradation. The goals of the experiments included here were to a) characterize gene expression in knee joint articular chondrocytes at various stages of development of OA (2 and 8 weeks after surgical induction of OA), and b) to establish trends in gene expression among groups of genes related to the TGF alpha-EGFR axis, over time, in OA. The model chosen to study these results has been previously validated (Appleton, CT et al, 2007, Arthritis Rheum) and used to describe similar gene expression results at a different time point (4 weeks) after induction of OA. The rat model of OA involves surgical destabilization of the knee joint, followed by forced low-intensity mobilization over several weeks; a sham surgery is used as the control (representing a healthy non-OA knee joint) wherein a surgical incision is made but not structural (i.e. ligamentous) modification is made to the joint. Altogether, our data indicate that TGF and CCL2 cooperate to drive cartilage degradation in osteoarthritis.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Mouse pancreas from wild type and MistKO animals were induced either with caerulein or saline as control and processed for RNA. Targets from three biological replicates of each were generated and the expression profiles were determined using Affymetrix Mouse Expression chips 430. Comparisons between the sample groups allow the identification of genes with differential expression patterns of genes which might contribute to pancreatitis.
Publication Title
Mice lacking the transcription factor Mist1 exhibit an altered stress response and increased sensitivity to caerulein-induced pancreatitis.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 28 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
While pathogen-induced immunity is comparatively well characterized, far less is known about plant defense responses to arthropod herbivores. To date, most molecular-genetic studies of plant-arthropod interactions have focused on insects. However, plant-feeding (phytophagous) mites are also pests of diverse plants, and mites induce different patterns of damage to plant tissues than do well-studied insects (e.g., Lepidopteran larvae or aphids). The two-spotted spider mite, Tetranychus urticae, is among the most significant mite pests in agriculture. T. urticae is an extreme generalist that has been documented on a staggering number of plant hosts (more than 1,100), and is renowned for the rapid evolution of pesticide resistance. To understand reciprocal interactions between T. urticae and a plant host at the molecular level, we examined mite herbivory using Arabidopsis thaliana. Despite differences in feeding guilds, we found that transcriptional responses of A. thaliana to mite herbivory generally resembled those observed for insect herbivores. In particular, defense to mites was mediated by jasmonic acid (JA) biosynthesis and signaling. Further, indole glucosinolates dramatically increased mite mortality and development times. Variation in both basal and activated levels of these defense pathways might also explain differences in mite damage and feeding success between A. thaliana accessions. On the herbivore side, a diverse set of genes associated with detoxification of xenobiotics was induced upon exposure to increasing levels of in planta indole glucosinolates. Our findings provide molecular insights into the nature of, and response to, herbivory for a representative of a major class of arthropod herbivores.
Publication Title
Reciprocal responses in the interaction between Arabidopsis and the cell-content-feeding chelicerate herbivore spider mite.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Lead exposure causes a variety of health effects, especially in children, that may include cognitive and behavioural problems. This study explores the mechanisms associated with this relationship by assessing alterations in gene expression of C57BL/6J pups treated with 50mg/kg lead compared to controls.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
C-type natriuretic peptide (CNP) has been recently identified as an important anabolic regulator of endochondral bone growth, but the molecular mechanism mediating these effects are not completely understood. Here we demonstrate that CNP activates the p38 MAP kinase pathway in chondrocytes and that pharmacological inhibition of p38 blocks the anabolic effects of CNP in a tibia organ culture system. We further show that CNP stimulates endochondral bone growth largely through expansion of the hypertrophic zone of the growth plate, while delaying mineralization. Both effects are reversed by p38 inhibition. We performed Affymetrix microarray analyses to identify CNP target genes in the organ culture system. These studies confirmed that hypertrophic chondrocytes are the main targets of CNP signaling in the growth plate, potentially because cGMP-dependent kinases I and II, important transducers of CNP signaling and are expressed at much higher levels in these cells than in other areas of the tibia. One of the genes most strongly induced by CNP was the Ptgs2 gene, encoding Cox2. Real-time PCR confirmed that Cox2 expression was induced by CNP in hypertrophic chondrocytes, but surprisingly in a p38-independent manner. Moreover, Cox2 inhibition in contrast to p38 inhibition - did not block the anabolic effects of CNP. In summary, our data identify novel target genes of CNP and demonstrate that the p38 pathway is a novel, essential mediator of CNP effects on endochondral ossification, with potential implications for numerous skeletal diseases.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Aberrant TGFbeta signalling is a hallmark of epithelial derived tumours. Signalling patterns can depend on the membrane trafficking and internalization of the TGFbeta receptors. Protein kinase C (PKC), particularly the atypical PKC isoforms, alter the trafficking of TGFbeta receptors and can alter TGFbeta induced gene expression.
Publication Title
aPKC alters the TGFβ response in NSCLC cells through both Smad-dependent and Smad-independent pathways.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Briefly, the well characterized female hES cell line H9 was allowed to differentiate into a clonally purified mortal splanchnopleuric mesodermal somatic cell line EN13. The EN13 line was subsequently virally reprogrammed back to an induced pluripotent state (we term re-H9) using OCT4, SOX2, KLF4 retroviral vectors creating isogenic lines of hESC, hiPSC and mortal cells. Our results reveal several important differences between embryo-derived H9 and the induced re-H9 stem cells. We find a dysregulation of genes involved in imprinting and altered expression of X-chromosome localized genes in re-H9 cells.
Publication Title
Suppression of the imprinted gene NNAT and X-chromosome gene activation in isogenic human iPS cells.
Sample Metadata Fields
Cell line
View Samples
GSE8488- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Objectives: To identify similarities and differences in gene expression data in the MEK/ERK and PI3K pathways and to determine how histone modification affects these same pathways.
Publication Title
Regulation of gene expression by PI3K in mouse growth plate chondrocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Objectives: To identify similarities and differences in gene expression data in the MEK/ERK and PI3K pathways and to determine how histone modification affects these same pathways. Goal: To identify and functionally characterize novel targets of these signaling pathways in the context of chondrocyte differentiation.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples