Transcriptomic signatures of cartilage ageing
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR206797_1.fastq.gz | Fastqsanger.gz | |||
| ERR206797_2.fastq.gz | Fastqsanger.gz | |||
| ERR206798_1.fastq.gz | Fastqsanger.gz | |||
| ERR206798_2.fastq.gz | Fastqsanger.gz | |||
| ERR206799_1.fastq.gz | Fastqsanger.gz |
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Project description:Equine cartilage from young and old donors was used for RNA-Seq analysis. The aim of the study was to identify differentially expressed cartilage transcripts in ageing in order to to characterize molecular mechanisms associated with age-related changes in
2014-01-11 | E-MTAB-1386 | biostudies-arrayexpress
Project description:IntroductionAge is an important factor in the development of osteoarthritis. Microarray studies provide insight into cartilage aging but do not reveal the full transcriptomic phenotype of chondrocytes such as small noncoding RNAs, pseudogenes, and microRNAs. RNA-Seq is a powerful technique for the interrogation of large numbers of transcripts including nonprotein coding RNAs. The aim of the study was to characterise molecular mechanisms associated with age-related changes in gene signatures.MethodsRNA for gene expression analysis using RNA-Seq and real-time PCR analysis was isolated from macroscopically normal cartilage of the metacarpophalangeal joints of eight horses; four young donors (4 years old) and four old donors (>15 years old). RNA sequence libraries were prepared following ribosomal RNA depletion and sequencing was undertaken using the Illumina HiSeq 2000 platform. Differentially expressed genes were defined using Benjamini-Hochberg false discovery rate correction with a generalised linear model likelihood ratio test (P < 0.05, expression ratios ± 1.4 log₂ fold-change). Ingenuity pathway analysis enabled networks, functional analyses and canonical pathways from differentially expressed genes to be determined.ResultsIn total, the expression of 396 transcribed elements including mRNAs, small noncoding RNAs, pseudogenes, and a single microRNA was significantly different in old compared with young cartilage (± 1.4 log2 fold-change, P < 0.05). Of these, 93 were at higher levels in the older cartilage and 303 were at lower levels in the older cartilage. There was an over-representation of genes with reduced expression relating to extracellular matrix, degradative proteases, matrix synthetic enzymes, cytokines and growth factors in cartilage derived from older donors compared with young donors. In addition, there was a reduction in Wnt signalling in ageing cartilage.ConclusionThere was an age-related dysregulation of matrix, anabolic and catabolic cartilage factors. This study has increased our knowledge of transcriptional networks in cartilage ageing by providing a global view of the transcriptome.
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Project description:Successful pregnancies require fine coordination among the reproductive organs. Reproductive research has focused on ovarian ageing, the uterus and oviduct have received much less attention; whether these organs age synchronously with the ovaries remains unclear. Here, we established a single-cell transcriptomic atlas of the ovary, oviduct, and uterus across the murine reproductive lifespan. Organ–organ communication patterns were identified using cell-specific hormone receptor analysis. The ageing hallmarks (including DNA damage, cellular senescence, and apoptosis, etc.) were evaluated for each cell type. Analysis of these ageing-related gene set scores combined with changes in morphology and molecular signatures revealed that the ovary aged earlier and faster than the oviduct and uterus; this was also confirmed in human reproductive tissues. Our single-cell transcriptomic atlas provides molecular insights into reproductive ageing and its asynchronization for the reproductive organs across the murine reproductive lifespan, which may reveal the causes of declining fertility at advanced ages.
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Project description:The musculoskeletal system is severely affected by the ageing process, with many tissues undergoing changes that lead to loss of function and frailty. Articular cartilage is susceptible to age related diseases, such as osteoarthritis. Applying RNA-Seq to young and old equine cartilage, we identified an over-representation of genes with reduced expression relating to extracellular matrix, degradative proteases, matrix synthetic enzymes, cytokines and growth factors in cartilage from older donors. Here we describe the contents and quality controls in detail for the gene expression and related results published by Peffers and colleagues in Arthritis Research and Therapy 2013 associated with the data uploaded to ArrayExpress (E-MTAB-1386).
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Project description:Transcriptomic signatures of telomerase-dependent and -independent ageing, un the zebrafish gut and brain
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Project description:Ageing related deficiency of miR-708-5p in osteoarthritic cartilage lesions
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Project description:Telomerase is best known for its role in the maintenance of telomere length and its implications for ageing and cancer. The mechanisms, kinetics and tissue-specificity underlying the protective or deleterious mechanisms of telomerase, however, remain largely unknown. Here, we sought to determine the telomerase-dependent and -independent transcriptomic changes with ageing, in the gut and brain, as examples of high and low proliferative tissues, respectively. We hypothesised this could shed light on common telomerase-dependent and -independent therapeutic targets aimed at preventing or ameliorating age-associated dysfunction in both tissues. For this, we used the zebrafish model which, similarly to humans, depends on telomerase for health- and life-span. We performed whole tissue RNA sequencing of gut and brain, in naturally aged zebrafish alongside prematurely aged telomerase null mutants (tert-/-), throughout their lifespan. Our study highlights stem cell exhaustion as the first main hallmark of ageing to be de-regulated in WT zebrafish gut and brain. Towards the end of life, altered intercellular communication becomes the main hallmark of ageing de-regulated in both gut and brain, and this is accelerated in both tissues, in the absence of telomerase. Finally, we identify 7 key gene changes common between the gut and brain at the early stages of ageing, highlighting potential early intervention therapeutic targets for preventing age-associated dysfunction in both tissues.
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Project description:Background: Meniscus tears are the most common injury in the knee and are associated with an increased risk of osteoarthritis (OA). The molecular profile of knees with meniscus tears is not well-studied. Therefore, to advance our understanding of the early response of the knee to injury, we compared the gene expression profile of meniscus and articular cartilage within the same knees following meniscus injury. Hypothesis/Purpose: To identify differences between the molecular signatures of meniscus and articular cartilage from knees with intact articular cartilage undergoing arthroscopic partial meniscectomy. Study Design: Descriptive laboratory study Methods: Patients (n=12) with a known isolated medial meniscus tear without any knee chondrosis or radiographic OA were consented prior to surgery. During arthroscopic partial meniscectomy, a sample of their injured meniscus and a sample of their articular cartilage off the medial femoral condyle were procured. The transcriptome signatures, as measured through Affymetrix microarray, were compared between the two tissues and underlying biological processes were explored computationally. Results: 3566 gene transcripts were differentially expressed between meniscus and articular cartilage. Gene transcripts down-regulated in articular cartilage were associated with extracellular matrix organization, wound healing, cell adhesion, and chemotaxis. Gene transcripts up-regulated in articular cartilage were associated with blood vessels morphogenesis and angiogenesis. Examples of individual genes with significant differences in expression between the two tissues include IBSP (23.76 fold; P < 0.001), upregulated in meniscus, and TREM1 (3.23 fold; P = 0.006), upregulated in meniscus. Conclusion: The meniscus and articular cartilage have distinct gene expression profiles in knees with meniscus tears and intact articular cartilage. Total RNA obtained from injured meniscus and normal articular cartilage from patients undergoing partial meniscectomy.
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