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The Journal of biological chemistry2014; 289(8); 4919-4927; doi: 10.1074/jbc.M113.511972

Proteomic analysis of tendon extracellular matrix reveals disease stage-specific fragmentation and differential cleavage of COMP (cartilage oligomeric matrix protein).

Abstract: During inflammatory processes the extracellular matrix (ECM) is extensively remodeled, and many of the constituent components are released as proteolytically cleaved fragments. These degradative processes are better documented for inflammatory joint diseases than tendinopathy even though the pathogenesis has many similarities. The aims of this study were to investigate the proteomic composition of injured tendons during early and late disease stages to identify disease-specific cleavage patterns of the ECM protein cartilage oligomeric matrix protein (COMP). In addition to characterizing fragments released in naturally occurring disease, we hypothesized that stimulation of tendon explants with proinflammatory mediators in vitro would induce fragments of COMP analogous to natural disease. Therefore, normal tendon explants were stimulated with IL-1β and prostaglandin E2, and their effects on the release of COMP and its cleavage patterns were characterized. Analyses of injured tendons identified an altered proteomic composition of the ECM at all stages post injury, showing protein fragments that were specific to disease stage. IL-1β enhanced the proteolytic cleavage and release of COMP from tendon explants, whereas PGE2 had no catabolic effect. Of the cleavage fragments identified in early stage tendon disease, two fragments were generated by an IL-1-mediated mechanism. These fragments provide a platform for the development of neo-epitope assays specific to injury stage for tendon disease.
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Publication Date: 2014-01-07 PubMed ID: 24398684PubMed Central: PMC3931053DOI: 10.1074/jbc.M113.511972Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

The research investigates the changes in the extracellular matrix (ECM) of injured tendons at different stages of disease, focusing specifically on how cartilage oligomeric matrix protein (COMP) is broken down. The findings indicate that the breakdown pattern of COMP through proteolytic cleavage is unique to specific stages of tendon disease and could potentially be used as a benchmark to identify the disease stage.

Objective of the Research

  • The study primarily aims to understand the proteomic composition of injured tendons during early and late stages of disease, observing how the protein COMP is cleaved differently at different stages. This is done by simulating an inflamed condition using proinflammatory mediators IL-1β and prostaglandin E2 in normal tendon samples.

Methodology and Observations

  • The experiment involved stimulating normal tendon samples with IL-1β and prostaglandin E2. These proinflammatory mediators were used to replicate the conditions of an inflamed tendon, thus enabling the researchers to investigate how they influence the breakdown and release of COMP.
  • Researchers found that the proteomic composition of the ECM in injured tendons changes at all stages post injury. These changes entailed protein fragments specific to the disease stage.
  • It was observed that IL-1β boosted the proteolytic cleavage and release of COMP from tendon samples, while PGE2 had no significant catabolic effect.
  • The researchers identified two fragments in early-stage tendon disease that were generated by an IL-1β mechanism, suggesting that these fragments could serve as unique indicators of the injury stage.

Significance of the Research

  • This research provides a deeper understanding of how tendinopathy progresses at a molecular level. The identification of stage-specific proteolytic cleavage patterns of COMP could potentially be used in the future as unique markers to diagnose the stage of tendon disease.
  • These findings could help in the development of disease-specific assays, or tests, which may facilitate early and accurate diagnosis of tendon diseases and thus enable prompt and effective treatment.

Cite This Article

APA
Dakin SG, Smith RK, Heinegård D, Önnerfjord P, Khabut A, Dudhia J. (2014). Proteomic analysis of tendon extracellular matrix reveals disease stage-specific fragmentation and differential cleavage of COMP (cartilage oligomeric matrix protein). J Biol Chem, 289(8), 4919-4927. https://doi.org/10.1074/jbc.M113.511972

Publication

The Journal of biological chemistry
ISSN: 1083-351X
NlmUniqueID: 2985121R
Country: United States
Language: English
Volume: 289
Issue: 8
Pages: 4919-4927

Researcher Affiliations

Dakin, Stephanie Georgina
  • From the Department of Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, United Kingdom and.
Smith, Roger Kenneth Whealands
    Heinegård, Dick
      Önnerfjord, Patrik
        Khabut, Areej
          Dudhia, Jayesh

            MeSH Terms

            • Amino Acid Sequence
            • Animals
            • Blotting, Western
            • Cartilage Oligomeric Matrix Protein / chemistry
            • Cartilage Oligomeric Matrix Protein / metabolism
            • Chromatography, Liquid
            • Culture Media
            • Dinoprostone / pharmacology
            • Extracellular Matrix / metabolism
            • Horses
            • Humans
            • Interleukin-1beta / pharmacology
            • Mass Spectrometry
            • Molecular Sequence Data
            • Proteomics / methods
            • Tendinopathy / metabolism
            • Tendinopathy / pathology
            • Tendons / drug effects
            • Tendons / metabolism
            • Tendons / pathology
            • Tissue Survival / drug effects

            Grant Funding

            • BB/F018258/1 / Biotechnology and Biological Sciences Research Council

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