Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA196707 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Osteoarthritis (OA) is a chronic, degenerative whole-joint disorder that interferes with quality of life in older individuals. Here, we report a high expression of ZDHHC11 in articular chondrocytes, which is downregulated in the degenerated cartilage of aged mice and OA patients. ZDHHC11 prevents chondrocyte senescence and fosters cartilage anabolism, culminating in an improved OA phenotype. Mice with Zdhhc11 deletion (Zdhhc11fl/fl) exacerbate OA progression in a destabilized medial meniscus (DMM) model.
2025-08-12 | PXD063537 | Pride
Project description:Objective Animal models of post-traumatic osteoarthritis (PTOA) recapitulate the pathological changes observed in human PTOA. Here we aimed to compare the cartilage transcriptome responses of a non-surgical, mechanically induced rupture of the anterior cruciate ligament (ACL) model and the surgical destabilisation of the medial meniscus (DMM) model. Methods Skeletally mature male C57Bl6 mice were subjected to either the non-surgical, mechanical ACL rupture or surgical DMM models and transcriptome profiling performed on micro-dissected cartilage at day 7 and 42 post-procedure, respectively; in general, naïve animals served as controls. MicroRNA profiling was also performed on the ACL rupture model. Expression levels of a miRNA of interest, miR-199-5p, were inhibited in primary human articular chondrocytes (HAC) with RNA-seq and 3’UTR assays used to identify and valid potential target genes. Results The number of differentially expressed genes between the two models were comparable and highly correlative (Spearman R =0.8, P<2.2E-16). Gene ontology enrichment analysis identified similarly enriched pathways, containing anabolic terms including ‘extracellular matrix organisation’ enriched for the upregulated genes. Within the ACL rupture miRNA transcriptome, miR-199-5p family members were amongst the most abundantly, and differentially expressed, which was replicated in the DMM cartilage by qRT-PCR. Inhibition of miR-199-5p in HAC led to a comparable transcriptome response to that observed in both human OA damaged vs intact cartilage and murine DMM cartilage datasets. Several genes, including GIT1, NCEH1, SOS2 and ECE1 were all experimentally verified as targets. Conclusion For the first time, we have characterised both the mRNA and miRNA articular cartilage signature in the ACL rupture model and demonstrated highly correlative responses with the DMM PTOA model. These data support the use of the ACL rupture model as a non-invasive alternative to DMM.
2024-10-01 | GSE232206 | GEO
Project description:Objective Animal models of post-traumatic osteoarthritis (PTOA) recapitulate the pathological changes observed in human PTOA. Here we aimed to compare the cartilage transcriptome responses of a non-surgical, mechanically induced rupture of the anterior cruciate ligament (ACL) model and the surgical destabilisation of the medial meniscus (DMM) model. Methods Skeletally mature male C57Bl6 mice were subjected to either the non-surgical, mechanical ACL rupture or surgical DMM models and transcriptome profiling performed on micro-dissected cartilage at day 7 and 42 post-procedure, respectively; in general, naïve animals served as controls. MicroRNA profiling was also performed on the ACL rupture model. Expression levels of a miRNA of interest, miR-199-5p, were inhibited in primary human articular chondrocytes (HAC) with RNA-seq and 3’UTR assays used to identify and valid potential target genes. Results The number of differentially expressed genes between the two models were comparable and highly correlative (Spearman R =0.8, P<2.2E-16). Gene ontology enrichment analysis identified similarly enriched pathways, containing anabolic terms including ‘extracellular matrix organisation’ enriched for the upregulated genes. Within the ACL rupture miRNA transcriptome, miR-199-5p family members were amongst the most abundantly, and differentially expressed, which was replicated in the DMM cartilage by qRT-PCR. Inhibition of miR-199-5p in HAC led to a comparable transcriptome response to that observed in both human OA damaged vs intact cartilage and murine DMM cartilage datasets. Several genes, including GIT1, NCEH1, SOS2 and ECE1 were all experimentally verified as targets. Conclusion For the first time, we have characterised both the mRNA and miRNA articular cartilage signature in the ACL rupture model and demonstrated highly correlative responses with the DMM PTOA model. These data support the use of the ACL rupture model as a non-invasive alternative to DMM.
2024-10-01 | GSE229510 | GEO
Project description:Objective Animal models of post-traumatic osteoarthritis (PTOA) recapitulate the pathological changes observed in human PTOA. Here we aimed to compare the cartilage transcriptome responses of a non-surgical, mechanically induced rupture of the anterior cruciate ligament (ACL) model and the surgical destabilisation of the medial meniscus (DMM) model. Methods Skeletally mature male C57Bl6 mice were subjected to either the non-surgical, mechanical ACL rupture or surgical DMM models and transcriptome profiling performed on micro-dissected cartilage at day 7 and 42 post-procedure, respectively; in general, naïve animals served as controls. MicroRNA profiling was also performed on the ACL rupture model. Expression levels of a miRNA of interest, miR-199-5p, were inhibited in primary human articular chondrocytes (HAC) with RNA-seq and 3’UTR assays used to identify and valid potential target genes. Results The number of differentially expressed genes between the two models were comparable and highly correlative (Spearman R =0.8, P<2.2E-16). Gene ontology enrichment analysis identified similarly enriched pathways, containing anabolic terms including ‘extracellular matrix organisation’ enriched for the upregulated genes. Within the ACL rupture miRNA transcriptome, miR-199-5p family members were amongst the most abundantly, and differentially expressed, which was replicated in the DMM cartilage by qRT-PCR. Inhibition of miR-199-5p in HAC led to a comparable transcriptome response to that observed in both human OA damaged vs intact cartilage and murine DMM cartilage datasets. Several genes, including GIT1, NCEH1, SOS2 and ECE1 were all experimentally verified as targets. Conclusion For the first time, we have characterised both the mRNA and miRNA articular cartilage signature in the ACL rupture model and demonstrated highly correlative responses with the DMM PTOA model. These data support the use of the ACL rupture model as a non-invasive alternative to DMM.
2024-10-01 | GSE232208 | GEO
Project description:Objective Animal models of post-traumatic osteoarthritis (PTOA) recapitulate the pathological changes observed in human PTOA. Here we aimed to compare the cartilage transcriptome responses of a non-surgical, mechanically induced rupture of the anterior cruciate ligament (ACL) model and the surgical destabilisation of the medial meniscus (DMM) model. Methods Skeletally mature male C57Bl6 mice were subjected to either the non-surgical, mechanical ACL rupture or surgical DMM models and transcriptome profiling performed on micro-dissected cartilage at day 7 and 42 post-procedure, respectively; in general, naïve animals served as controls. MicroRNA profiling was also performed on the ACL rupture model. Expression levels of a miRNA of interest, miR-199-5p, were inhibited in primary human articular chondrocytes (HAC) with RNA-seq and 3’UTR assays used to identify and valid potential target genes. Results The number of differentially expressed genes between the two models were comparable and highly correlative (Spearman R =0.8, P<2.2E-16). Gene ontology enrichment analysis identified similarly enriched pathways, containing anabolic terms including ‘extracellular matrix organisation’ enriched for the upregulated genes. Within the ACL rupture miRNA transcriptome, miR-199-5p family members were amongst the most abundantly, and differentially expressed, which was replicated in the DMM cartilage by qRT-PCR. Inhibition of miR-199-5p in HAC led to a comparable transcriptome response to that observed in both human OA damaged vs intact cartilage and murine DMM cartilage datasets. Several genes, including GIT1, NCEH1, SOS2 and ECE1 were all experimentally verified as targets. Conclusion For the first time, we have characterised both the mRNA and miRNA articular cartilage signature in the ACL rupture model and demonstrated highly correlative responses with the DMM PTOA model. These data support the use of the ACL rupture model as a non-invasive alternative to DMM.
2024-10-01 | GSE229437 | GEO
Project description:Osteoarthritis (OA) is typically characterized by progressive cartilage breakdown, subchondral bone remodeling, osteophyte formation and low-grade joint inflammation. Accumulative evidence demonstrates that cartilage fibrosis and the resulting degradation of extracellular matrix are implicated in the late-stage pathology of OA. However, the mechanisms underlying this degenerative joint disease remain largely undefined.We isolated articular cartilage from control-sham, control-DMM and cKOAcan(chondrocyte conditional ZEB1 knockout mice)-DMM mice and performed scRNA-seq analysis.
2025-09-03 | GSE306471 | GEO
Project description:Objective: We used the destabilization of the medial meniscus (DMM) model to identify temporal changes in DNA methylation patterns associated with structural and transcriptomic changes in cartilage during osteoarthritis (OA) progression. Methods: RNA sequencing (RNAseq) and Reduced Representation Oxidative Bisulfite Sequencing (RRoxBS) analyses were done in total RNA and DNA obtained from micro-dissected cartilage at 4 and 12 weeks after DMM surgery. Murine and human primary chondrocytes were used to evaluate the cytokine- and methylation-dependent changes in the expression of Lrrc15, and its contribution to IL-1beta-induced changes in chondrocytes. Results: We identified time-dependent alterations in epigenomic patterns in cartilage after DMM, with significant changes in 5mC and 5hmC methylation comparing samples retrieved at 4 and 12 weeks after surgery. Integration of RNAseq and RRoxBS datasets identified Lrrc15 as a hypomethylated gene with increased expression at 4 weeks after surgery. We confirmed LRRC15 immunostaining in OA cartilage, and experiments in human and murine primary chondrocytes showed that the expression of Lrrc15 is DNA methylation-dependent and induced by IL1beta and TNFalfa in vitro. Knockdown experiments showed that Lrrc15 contributes to the IL1beta-driven expression of catabolic genes relevant to OA, including Mmp13. Significance: Our integrative analyses showed that the structural progression of OA is accompanied by transcriptomic and dynamic epigenomic changes in articular cartilage. We found that Lrrc15 is differentially methylated and expressed in OA cartilage, and that it may contribute to the cytokine-driven responses of OA chondrocytes. A better understanding of the role of Lrrc15 in cartilage homeostasis and osteoarthritis may help us uncover targets with therapeutic potential.
2021-09-01 | GSE175486 | GEO
Project description:Osteoarthritis (OA) is a chronic, degenerative whole-joint disorder that interferes with quality of life in older individuals. Here, we report a high expression of ZDHHC11 in articular chondrocytes, which is downregulated in the degenerated cartilage of aged mice and OA patients. ZDHHC11 prevents chondrocyte senescence and fosters cartilage anabolism, culminating in an improved OA phenotype. Mice with Zdhhc11 deletion (Zdhhc11fl/fl) exacerbate OA progression in a destabilized medial meniscus (DMM) model. Specifically, we identify ZDHHC11 as a key palmitoyltransferase, the depletion of which leads to GNB2-dependent E3 ubiquitin ligase-mediated proteasomal degradation of APOD.
2025-08-12 | PXD063859 | Pride
Project description:Osteoarthritis (OA) is a chronic, degenerative whole-joint disorder that interferes with quality of life in older individuals. Here, we report a high expression of ZDHHC11 in articular chondrocytes, which is downregulated in the degenerated cartilage of aged mice and OA patients. ZDHHC11 prevents chondrocyte senescence and fosters cartilage anabolism, culminating in an improved OA phenotype. Mice with Zdhhc11 deletion (Zdhhc11fl/fl) exacerbate OA progression in a destabilized medial meniscus (DMM) model. Specifically, we identify ZDHHC11 as a key palmitoyltransferase, the depletion of which leads to GNB2-dependent E3 ubiquitin ligase-mediated proteasomal degradation of APOD.
2025-08-12 | PXD063864 | Pride
Project description:Osteoarthritis (OA) is a chronic, degenerative whole-joint disorder that interferes with quality of life in older individuals. Here, we report a high expression of ZDHHC11 in articular chondrocytes, which is downregulated in the degenerated cartilage of aged mice and OA patients. ZDHHC11 prevents chondrocyte senescence and fosters cartilage anabolism, culminating in an improved OA phenotype. Mice with Zdhhc11 deletion (Zdhhc11fl/fl) exacerbate OA progression in a destabilized medial meniscus (DMM) model. Specifically, we identify ZDHHC11 as a key palmitoyltransferase, the depletion of which leads to GNB2-dependent E3 ubiquitin ligase-mediated proteasomal degradation of APOD.
2025-08-12 | PXD063840 | Pride