Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA148643 | ENA |
REPOSITORIES: ENA
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Project description:Pregnane X receptor knockout mice display aging-dependent wearing of articular cartilage
| PRJNA258189 | ENA
Project description:Steroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and the intestine. They function as xenobiotic sensors by inducing genes involved in detoxification and drug excretion. Recent evidence showed that SXR and PXR are also expressed in bone tissue where they mediate bone metabolism. Here we report that systemic deletion of PXR results in aging-dependent wearing of articular cartilage of knee joints. Histomorphometrical analysis showed remarkable reduction of width and an enlarged gap between femoral and tibial articular cartilage in PXR knockout mice. We hypothesized that genes induced by SXR in chondrocytes have a protective effect on articular cartilage and identified Fam20a (family with sequence similarity 20a) as an SXR-dependent gene induced by the known SXR ligands, rifampicin and vitamin K2. Lastly, we demonstrated the biological significance of Fam20a expression in chondrocytes by evaluating osteoarthritis-related gene expression of primary articular chondrocytes. Consistent with epidemiological findings, our findings indicate that SXR/PXR protects against aging-dependent wearing of articular cartilage and that ligands for SXR/PXR have potential role in preventing osteoarthritis caused by aging.
2015-03-31 | GSE60401 | GEO
Project description:Aberrant Calreticulin expression in articular cartilage of Dio2 deficient mice
| PRJNA315260 | ENA
Project description:Kindlin-2 conditional knockout mouse articular cartilage Raw sequence reads
| PRJNA772806 | ENA
Project description:Steroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and the intestine. They function as xenobiotic sensors by inducing genes involved in detoxification and drug excretion. Recent evidence showed that SXR and PXR are also expressed in bone tissue where they mediate bone metabolism. Here we report that systemic deletion of PXR results in aging-dependent wearing of articular cartilage of knee joints. Histomorphometrical analysis showed remarkable reduction of width and an enlarged gap between femoral and tibial articular cartilage in PXR knockout mice. We hypothesized that genes induced by SXR in chondrocytes have a protective effect on articular cartilage and identified Fam20a (family with sequence similarity 20a) as an SXR-dependent gene induced by the known SXR ligands, rifampicin and vitamin K2. Lastly, we demonstrated the biological significance of Fam20a expression in chondrocytes by evaluating osteoarthritis-related gene expression of primary articular chondrocytes. Consistent with epidemiological findings, our findings indicate that SXR/PXR protects against aging-dependent wearing of articular cartilage and that ligands for SXR/PXR have potential role in preventing osteoarthritis caused by aging. ADC5 cells were infected with adeno-SXR or adeno-DsRed and cultured in phenol red-free DMEM with charcoal/dextran-treated FCS (5%) containing rifampicin (10 μM), vitamin K2 (10 μM), or ethanol. Total RNA was extracted from the cells using the ToTALLY RNA Kit (Ambion, Austin, TX). Profiling of mRNA was performed on Affymetrix Mouse Gene 1.0 ST arrays (Affymetrix Inc., Santa Clara, USA) according to the Gene Chip labeling assay manual version 4.
2015-03-31 | E-GEOD-60401 | biostudies-arrayexpress
Project description:Objective : To study molecular changes in the articular cartilage and subchondral bone of the tibial plateau from mice deficient in frizzled related protein (Frzb) compared to wild-type mice by transcriptome analysis. Methods : Gene-expression analysis of the articular cartilage and subchondral bone of 3 wild-type and 3 Frzb-/- mice was performed by microarray. Pathway analysis of differentially expressed genes between 3 wild-type and 2 Frzb-/- samples was explored with PANTHER, DAVID and GSEA bioinformatics tools. Activation of the WNT pathway was analyzed using western blot. The effects of Frzb gain and loss of function on chondrogenesis and cell proliferation was examined using ATDC5 micromasses and mouse ribcage chondrocytes. Results : Extracellular matrix-associated integrin and cadherin pathways, as well as WNT pathway genes were upregulated in Frzb-/- samples. Several WNT receptors, target genes, and other antagonists were upregulated, but no difference in active β-catenin was found. Analysis of ATDC5 cell micromasses overexpressing FRZB indicated an upregulation of aggrecan and Col2a1, and downregulation of molecules related to damage and repair in cartilage, Col3a1 and Col5a1. Silencing of Frzb resulted in downregulation of aggrecan and Col2a1. Pathways associated with cell cycle were downregulated. Ribcage chondrocytes derived from Frzb-/- mice showed decreased proliferation compared to wild-type cells. Conclusions : Our analysis provides evidence for tight regulation of WNT signaling, shifts in extracellular matrix components and effects on cell proliferation and differentiation in the articular cartilage - subchondral bone unit in Frzb-/- mice. These data further support an important role for FRZB in joint homeostasis and highlight the complex biology of WNT signaling in the joint. Gene-expression analysis of the articular cartilage and subchondral bone of 3 wild-type and 3 Frzb-/- mice was performed by microarray. Pathway analysis of differentially expressed genes between 3 wild-type and 2 Frzb-/- samples was explored with PANTHER, DAVID and GSEA bioinformatics tools.
2012-01-12 | E-GEOD-33656 | biostudies-arrayexpress
Project description:The global gene expression profile of superficial zone articular cartilage in P1 wildtype and Prg4 transgenic mice
| PRJNA186956 | ENA
Project description:A genetic association between the ANP32A gene and osteoarthritis has been suggested. We compared transcriptome profiles of the articular cartilage and subchondral bone from mice deficient in ANP32A with wild-type mice to get insights into the role of ANP32A in the pathogenesis of ostearthritis.
2018-06-07 | GSE108036 | GEO
Project description:Focal lesions of articular cartilage give rise to pain and reduced joint function and may, if left untreated, lead to osteoarthritis. Implantation of in vitro generated, scaffold-free autologous cartilage discs may represent the best treatment option. Here we compare articular chondrocytes (ACs) and bone marrow-derived mesenchymal stromal cells (MSCs) for their ability to make scaffold-free cartilage discs.
2023-02-07 | PXD029434 | Pride
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
2014-12-04 | GSE61417 | GEO