Transcriptomic signatures of cartilage ageing
Ontology highlight
ABSTRACT:
ORGANISM(S): Equus caballus
SUBMITTER: Mandy Peffers
PROVIDER: E-MTAB-1386 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:A tissue survey of gene expression was conducted using microarray-based transcriptional profiling to compare equine articular cartilage to 10 other normal adult horse tissues. The ten comparative tissues were bladder, cerebellum, kidney, liver, lung, lymph node, muscle, placental villous, spleen, and testis. Messenger RNA transcriptome comparisons were conducted between equine articular cartilage and ten other body tissues using a 9413 element equine-specific cDNA microarray and a two-color dye-swap experimental design. After scanning, the median intensities adjusted for background were entire chip Lowess-normalized for each individual slide. Quantile regression was used to estimate the conditional quantile of the M and A log ratios given the observed average log intensity. Briefly, a nonparametric approach was used to reveal the relationship between percentiles of M and A, where M is log2 (R/G) and A is 0.5 log2 (RG) with R representing expression in articular cartilage and G representing expression in the comparative tissue. The quantile regression was fit using a B-spline with 5 fixed nodes. The 1st, 5th, 10th, 20th, 50th, 80th, 90th, 95th, and 99th conditional quantiles were estimated. For each observed gene intensity in a given tissue comparison, the normal quantile was used as the cartilage-specificity in place of the corresponding estimated regression quantile.
2011-01-27 | E-GEOD-23862 | biostudies-arrayexpress
Project description:Objective. Identify novel genes and pathways specific to superficial (SZ), middle (MZ) and deep zones (DZ) of normal articular cartilage. Methods. Articular cartilage was obtained from knees of 4 normal human donors. The cartilage zones were dissected on a microtome. RNA was analyzed on human genome arrays. Data obtained with human tissue were compared to bovine cartilage zone specific DNA arrays. Genes differentially expressed between zones were evaluated using direct annotation for structural or functional features, and by enrichment analysis for integrated pathways or functions. Results. The greatest differences were observed between SZ and DZ in both human and bovine cartilage. The MZ was transitional between the SZ and DZ and thereby shared some of the same pathways as well as structural/functional features of the adjacent zones. Cellular functions and biological processes enriched in the SZ relative to the DZ, include most prominently ECM receptor interactions, cell adhesion molecules, regulation of actin cytoskeleton, ribosome-related functions and signaling aspects such as Interferon gamma, IL4, CDC42Rac and Jak-Stat. Two pathways were enriched in the DZ relative to the SZ, including PPARG and EGFR_SMRTE. Conclusion. These differences in cartilage zonal gene expression identify new markers and pathways that govern the unique differentiation status of chondrocyte subpopulations. 6 samples, 2 bovine donors, 3 conditions each donor (SZ, MZ and DZ), 0 donor replicates, comparisons made between SZ, MZ and DZ to identify differentially expressed genes.
2012-07-31 | E-GEOD-39796 | biostudies-arrayexpress
Project description:Short-read NGS technology (SOLIDTM, Life Technologies) was used to establish a comprehensive repertoire of miRNA expressed in either equine cartilage or subchondral bone. Undamaged cartilage and subchondral bone samples from 10-month Anglo-Arabian foals affected by osteochondrosis (OC) were analyzed and compared with samples from healthy foals. Samples were also subjected or not to an experimental mechanical loading to evaluate the role of miRNAs in the regulation of mechano-transduction pathways. Epiphyseal cartilage and subchondral bone miRNome were defined, including about 300 new miRNAs. Differentially expressed miRNAs were identified between bone and cartilage from healthy and OC foals, as well as after the experimental mechanical loading, suggesting that miRNAs play a role in equine OC physiopathology and in the cellular response to biomechanical stress in cartilage and bone.
2014-08-24 | E-MTAB-2736 | biostudies-arrayexpress
Project description:Objective Human primary articular chondrocytes (hPACs) are routinely isolated from articular cartilage and for pre-clinical OA research. Collagenase digest of tissue is an essential step, yet the impact of enzymatic incubation on the phenotype of hPACs is unclear. We aim to delineate this through proteomic and transcriptomic analysis. Design hPACs were isolated from human knee cartilage (N=4) with and without prior fixation. Proteomes were quantified using LC-MS/MS. The Proteome Ruler was employed to estimate protein copy numbers and cell protein masses. Significant differences in protein intensities were determined using paired t-testing and Benjamini-Hochberg correction. Proteomic data were integrated with existing transcriptomes (GSE217871) of hPACs and ground cartilage tissue. Results Collagenase treatment resulted in a 10% increase in protein mass/cell (P=0.06). Seven percent of the proteome (498 proteins) significantly changed (Padj. = 4.5x10-4 - 0.049). Pathway analysis revealed depletion of FOXO signaling terms (FDR = 0.049 – 0.024), and enrichment of ribosomal RNA processing terms (FDR = 0.025 – 2.9x10-11). Transcriptomic anlaysis revealed 3937 differentially expressed genes (P.adj<0.05), of which 97% of differentially-expressed proteins overlapped (R2 =0.83). Propidium iodide staining followed by flow-assisted cell sorting (FACS) (N=3) did not identify significant differences in cell cycle between fixed and unfixed chondrocytes (all P>0.05). Conclusions We identified shifts in the proteome and transcriptome of hPACs following collagenase digest, supporting use of tissue fixation before extracting nucleic acids for analysis. Despite widespread expression changes, hPACs retain their chondrocyte phenotype. These datasets and analyses will serve as a valuable resource for the OA research community.
2025-10-20 | PXD064948 | Pride
Project description:Objective. Identify novel genes and pathways specific to superficial (SZ), middle (MZ) and deep zones (DZ) of normal articular cartilage. Methods. Articular cartilage was obtained from knees of 4 normal human donors. The cartilage zones were dissected on a microtome. RNA was analyzed on human genome arrays. Data obtained with human tissue were compared to bovine cartilage zone specific DNA arrays. Genes differentially expressed between zones were evaluated using direct annotation for structural or functional features, and by enrichment analysis for integrated pathways or functions. Results. The greatest differences were observed between SZ and DZ in both human and bovine cartilage. The MZ was transitional between the SZ and DZ and thereby shared some of the same pathways as well as structural/functional features of the adjacent zones. Cellular functions and biological processes enriched in the SZ relative to the DZ, include most prominently ECM receptor interactions, cell adhesion molecules, regulation of actin cytoskeleton, ribosome-related functions and signaling aspects such as Interferon gamma, IL4, CDC42Rac and Jak-Stat. Two pathways were enriched in the DZ relative to the SZ, including PPARG and EGFR_SMRTE. Conclusion. These differences in cartilage zonal gene expression identify new markers and pathways that govern the unique differentiation status of chondrocyte subpopulations. 12 samples, 4 donors, 3 conditions each donor (SZ, MZ and DZ), 0 donor replicates, comparisons made between SZ, MZ and DZ to identify differentially expressed genes.
2012-07-31 | E-GEOD-39795 | biostudies-arrayexpress
Project description:The objective was to study the time-course effects of interleukin-1β (IL-1β) on equine articular cartilage, with the aim to identify genes of relevance for cartilage pathology in osteoarthritis. Changes in gene expression related to inflammation, extracellular matrix, and phenotypic alterations was studied.
2018-05-02 | GSE100083 | GEO
Project description:Transcriptomic signatures of cartilage ageing
| PRJEB1185 | ENA
Project description:Successfully replacing damaged cartilage with tissue-engineered constructs requires integration with the host tissue and could benefit from leveraging the native tissue's intrinsic healing capacity; however, efforts are limited by a poor understanding of how cartilage repairs minor defects. Here, we investigated the conditions that foster natural cartilage tissue repair to identify strategies that might be exploited to enhance the integration of engineered/ grafted cartilage with host tissue. We damaged porcine articular cartilage explants and using a combination of pulsed SILAC-based proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies reveal that integration of damaged cartilage surfaces is not driven by neo-matrix synthesis, but rather local depletion of proteoglycans. ADAMTS4 expression and activity are upregulated in injured cartilage explants, but integration could be reduced by inhibiting metalloproteinase activity with TIMP3. These observations suggest that catabolic enzyme-mediated proteoglycan depletion likely allows existing collagen fibrils to undergo cross-linking, fibrillogenesis, or entanglement, driving integration. Catabolic enzymes are often considered pathophysiological markers of osteoarthritis. Our findings suggest that damage-induced upregulation of metalloproteinase activity may be a part of a healing response that tips towards tissue destruction under pathological conditions and in osteoarthritis, but could also be harnessed in tissue engineering strategies to mediate repair. Statement of significance: Cartilage tissue engineering strategies require graft integration with the surrounding tissue; however, how the native tissue repairs minor injuries is poorly understood. We applied pulsed SILACbased proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies to a porcine cartilage explant model and found that integration of damaged cartilage surfaces is driven by catabolic enzyme-mediated local depletion of proteoglycans. Although catabolic enzymes have been implicated in cartilage destruction in osteoarthritis, our findings suggest that damage-induced upregulation of metalloproteinase activity may be a part of a healing response that tips towards tissue destruction under pathological conditions. They also suggest that this natural cartilage tissue repair process could be harnessed in tissue engineering strategies to enhance the integration of engineered cartilage with host tissue.
2022-07-18 | PXD035246 | Pride
Project description:Equine cartilage and bone miRNA repertoires
| PRJEB7060 | ENA
Project description:Fetal cartilage fully regenerates following injury while in adult mammals cartilage injury leads to osteoarthritis (OA). OA is characterized by cartilage breakdown and joint inflammation and associated with significant pain and socioeconomic costs. As no clinically satisfactory treatment is available to date, disease-modifying therapies aimed to achieve cartilage regeneration are urgently required. The inherent regeneration potential of fetal individuals may hold answers to this unmet need. Therefore, to characterize the differences in fetal and adult response to cartilage injury, we carried out histology and comprehensive proteome analyses on fetal (day 80/150-day gestation) and adult cartilage samples one (fetal samples) and three (adult and fetal samples) days after surgical induction of a full-thickness cartilage lesion. In addition, proteins secreted by inflamed fetal MSCs in vitro were compared with the in vivo response to injury to evaluate their therapeutic potential. Histology of synovial samples revealed the presence of neutrophils one day post injury (p.i.) and an influx of macrophages into the subsynovial tissue on day 3 p.i. in fetal samples. In contrast, adult synovial samples showed invasion of neutrophils on day 3 p.i. Activation and migration of Iba1+- macrophages of the synovial lining was observed both in fetal and adult animals. Comparative mass spectrometry revealed 57 proteins significantly up-regulated (> 2FC, FDR<0.05), and 67 proteins significantly down-regulated (<-2 FC) upon injury in adults. Neutrophil-related proteins and acute phase proteins were the two major upregulated protein groups in adult cartilage following injury compared to fetal sheep. In contrast, several immunomodulating proteins and growth factors were significantly higher expressed in the fetus than the adult. Comparison of the in vitro MSCs with the in vivo fetal proteome revealed shared upregulation of 17 proteins, which were considered to be of potential therapeutic interest. The results of this study support our molecular understanding of successful fetal cartilage healing and new therapeutic strategies to induce regeneration in adult articular cartilage by modulating the inflammatory environment. The shared protein upregulation in fetal cartilage in vivo and in fetal MSCS during in vitro inflammation supports the possible therapeutic potential of these factors in specific and fetal MSCs in general.
2022-02-17 | PXD027486 | Pride