Comparative analysis of cartilage tissue from ANP32A knockout mice and wildtype C57/Bl6 mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE108036 | GEO | 2018/06/07
REPOSITORIES: GEO
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Project description:Articular cartilage is deprived of blood vessels and nerves, and the only cells residing in this tissue are chondrocytes. The molecular properties of the articular cartilage and the architecture of the extracellular matrix demonstrate a complex structure that differentiates on the depth of tissue. Osteoarthritis (OA) is a degenerative joint disease, the most common form of arthritis, affecting the whole joint. It is associated with ageing and affects the joints that have been continually stressed throughout life including the knees, hips, fingers, and lower spine region. OA is a multifactorial condition of joint characterised by articular cartilage loss, subchondral bone sclerosis, and inflammation leading to progressive joint degradation, structural alterations, loss of mobility and pain. Articular cartilage biology is well studied with a focus on musculoskeletal diseases and cartilage development. However, there are relatively few studies focusing on zonal changes in the cartilage during osteoarthritis.
2022-05-19 | PXD029116 | Pride
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:Comparative analysis of cartilage tissue from ANP32A knockout mice and wildtype C57/Bl6 mice
| PRJNA422267 | ENA
Project description:Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage loss, bone remodeling, synovial inflammation, and significant joint pain, often resulting in disability. Injury to the synovial joint such as the anterior cruciate ligament (ACL) tear is the major cause of OA in young adults. Currently, there are no approved therapies available to prevent joint degeneration or rebuild articular cartilage destroyed by OA, primarily because our understanding of the cellular and molecular changes that contribute to joint damage is very limited. The synovial joint is a complex structure composed of several tissues including articular cartilage, subchondral bone, synovium, synovial fluid, and tensile tissues including tendons and ligaments. In the present study, using single-cell RNA sequencing (scRNA-seq), we examined the cellular heterogeneity in articular cartilage from mouse knee joints and determined the knee joint injury-induced early molecular changes in the chondrocytes that could contribute to OA.
2021-06-19 | GSE172500 | GEO
Project description:Osteoarthritis (OA) is a joint condition associated with articular cartilage loss, low-grade synovitis and alterations in subchondral bone and periarticular tissues. In OA, the interest for mesenchymal stem cell (MSC)-EV therapeutic applications has increased. We have assessed the immunomodulary properties of adipose-derived MSCs (AD-MSCs) microvesicles (MV) and exosomes (EX) in interleukin (IL)-1β stimulated OA chondrocytes and cartilage explants and characterized them by mass spectrometry in order to uncover novel mediators in (AD-MSC)-EV immunomodulation.
2022-02-23 | PXD009077 | Pride
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: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.
2012-01-12 | GSE33656 | GEO
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:Full thickness articular cartilage lesions with penetration into the subchondral bone fill with fibrocartilage-like repair tissue. However, the repair tissue has compromised structural and biomechanical properties relative to normal articular cartilage. The objective of this study was to evaluate transcriptome differences between normal articular cartilage and repair tissue. Bilateral one-cm2 full-thickness lesions were made in the articular surface of the distal femurs of four adult horses followed by subchondral microfracture. Four months postoperatively, repair tissue from the lesion site and grossly normal articular cartilage from each stifle were collected. Total RNA was isolated from tissue samples, linearly amplified, and applied to a 9367-probeset equine-specific cDNA microarray. Eight paired comparisons matched by limb and horse were made with a dye-swap experimental design. Comparisons were validated by histological analysis and quantitative real-time polymerase chain reaction (qPCR). Statistical analysis revealed 3,327 (35.2%) differentially expressed probesets. Biomarkers typically associated with normal articular cartilage and fibrocartilage repair tissue corroborate earlier studies. Other changes in gene expression previously unassociated with cartilage repair were also revealed and validated by qPCR. The magnitude of divergence in transcriptional profiles between normal chondrocytes and the cells that populate repair tissue reveal substantial functional differences between these two cell populations. At the four-month postoperative time point, the relative deficiency within repair tissue of transcripts from genes which typically define articular cartilage indicate that while cells occupying the lesion might be of mesenchymal origin, they have not recapitulated differentiation to the chondrogenic phenotype of normal articular chondrocytes.
2009-09-10 | GSE11760 | GEO
Project description:To date, all of the prior osteoarthritic microarray studies in human tissue have focused on the overlying articular cartilage, meniscus, or synovium but not the underlying subchondral bone. In our previous study, our group developed a methodology for high quality RNA isolation from site-matched cartilage and bone from human knee joints, which allowed us to perform candidate gene expression analysis on the subchohndral bone (published on Osteoarthritis and Cartilage on Dec/5/2012 (doi: 10.1016/j.joca.2012.11.016). To the best of our knowledge, the current study is the first to successfully perform whole-genome microarray profiling analyses of human osteoarthritic subchondral bone. We believe our comprehensive microarray results can improve the understanding of the pathogenesis of osteoarthritis and could further contribute to the development of new biomarker and therapeutic strategies in osteoarthritis.
2013-10-24 | GSE51588 | GEO