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Home/Equine Research Bank/Arthritis Res Ther/Transcriptomic signatures in cartilage ageing.
Arthritis research & therapy2013; 15(4); R98; doi: 10.1186/ar4278

Transcriptomic signatures in cartilage ageing.

Abstract: Age 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. Methods: RNA 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. Results: In 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. Conclusions: There 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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Publication Date: 2013-08-23 PubMed ID: 23971731PubMed Central: PMC3978620DOI: 10.1186/ar4278Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research focuses on the molecular mechanisms associated with age-related changes in cartilage by studying the gene expression of chondrocytes, and it suggests age-related dysregulation of matrix, anabolic and catabolic cartilage factors.

Research Methodology

  • The researchers conducted a study using RNA-Seq to analyse the gene expression in chondrocytes taken from the cartilage of eight horses, split evenly between young (4 years old) and old (>15 years old) subjects.
  • Ribosomal RNA was depleted, and their RNA sequences were prepared in libraries and sequenced using the Illumina HiSeq 2000 platform, a high-throughput sequencing system.
  • To establish which gene expressions were significantly different between old and young cartilage, the researchers used the Benjamini-Hochberg procedure. This method corrects for false discovery rate in multiple testing, using a generalised linear model likelihood ratio test.

Results

  • From this research, the scientists discovered differential expression in 396 transcribed elements in old and young cartilage, including mRNAs, small noncoding RNAs, pseudogenes, and a single microRNA.
  • 93 transcribed elements were found at higher levels, and 303 were found at lower levels in the older cartilage.
  • They found 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.
  • Wnt signalling, a group of signal transduction pathways made of proteins that pass signals into a cell through cell surface receptors, was also reduced in ageing cartilage.

Conclusion

  • The study concluded that there is an age-related dysregulation or imbalance of matrix, anabolic and catabolic cartilage factors which may contribute to the development of osteoarthritis.
  • This research enhances the understanding of transcriptional networks in cartilage ageing by providing a global view of the transcriptome. This could pave the way for further studies on the development of new therapies for osteoarthritis.

Cite This Article

APA
Peffers M, Liu X, Clegg P. (2013). Transcriptomic signatures in cartilage ageing. Arthritis Res Ther, 15(4), R98. https://doi.org/10.1186/ar4278

Publication

Arthritis research & therapy
ISSN: 1478-6362
NlmUniqueID: 101154438
Country: England
Language: English
Volume: 15
Issue: 4
Pages: R98

Researcher Affiliations

Peffers, Mandy
    Liu, Xuan
      Clegg, Peter

        MeSH Terms

        • Aging / genetics
        • Animals
        • Cartilage / pathology
        • Gene Expression Profiling / methods
        • High-Throughput Nucleotide Sequencing / methods
        • Horses
        • Osteoarthritis / genetics
        • Osteoarthritis / pathology
        • Polymerase Chain Reaction
        • Real-Time Polymerase Chain Reaction
        • Sequence Analysis, RNA / methods
        • Transcriptome

        Grant Funding

        • MR/K006312/1 / Medical Research Council
        • WT088557MA / Wellcome Trust

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