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Home / Equine Research Bank / J Orthop Res / Characterization of neopeptides in equine articular cartilag...
Journal of orthopaedic research : official publication of the Orthopaedic Research Society2015; 34(1); 106-120; doi: 10.1002/jor.22963

Characterization of neopeptides in equine articular cartilage degradation.

Abstract: Osteoarthritis is characterized by a loss of extracellular matrix that leads to cartilage degradation and joint space narrowing. Specific proteases, including the aggrecanases ADAMTS-4 and matrix metalloproteinase 3, are important in initiating and promoting cartilage degradation in osteoarthritis. This study investigated protease-specific and disease-specific cleavage patterns of particular extracellular matrix proteins by comparing new peptide fragments, neopeptides, in specific exogenous protease-driven digestion of a crude cartilage proteoglycan extract and an in-vitro model of early osteoarthritis. Additionally, equine cartilage explants were treated with interleukin-1 and the media collected. Proteolytic cleavage products following trypsin digestion were then identified using tandem mass spectrometry. Complete sequences of proteolytically cleaved neopeptides were determined for the major cartilage proteoglycans aggrecan, biglycan, decorin, fibromodulin plus cartilage oligomeric matrix protein. The generation of neopeptides varied with enzyme specificity; however, some peptides were common to all samples. Previous known and novel cleavage sites were identifies. The identification of novel peptide fragments provides a platform for the development of antibodies that could assist in the identification of biomarkers for osteoarthritis (OA), as well as the identification of basic biochemical processes underlying OA.
© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
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Publication Date: 2015-07-07 PubMed ID: 26124002PubMed Central: PMC4737130DOI: 10.1002/jor.22963Google Scholar: Lookup
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  • 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.

This research investigates how specific proteins are broken down in horse cartilage, leading to osteoarthritis. By examining newly created peptide fragments (neopeptides), the study uncovers patterns of cartilage degradation, which could point towards ways to detect and understand osteoarthritis.

Understanding Osteoarthritis in Horses

  • Osteoarthritis, a condition where the cartilage that acts as a cushion between joints begins to degenerate, can lead to loss of joint function and pain.
  • In horses, this condition can greatly undermine their performance and overall quality of life.
  • At the cellular level, this breakdown occurs when certain enzymes (proteases) begin to degrade extracellular matrix proteins.
  • Two prominent enzymes in this process are identified as ADAMTS-4 and matrix metalloproteinase 3.

Protease-Specific and Disease-Specific Cleavage Patterns

  • Using an in-vitro model of early osteoarthritis, the research sought to understand the cleavage patterns of these proteases in relation to specific extracellular matrix proteins.
  • The main method of examination was through the identification of neopeptides – fragments of proteins created through the enzymatic breakdown process.
  • The decomposition process was simulated in a laboratory setting with crude cartilage proteoglycan extracts exposed to specific exogenous proteases.

Exploring Neopeptides and Cartilage Proteoglycans

  • Mass spectrometry was used to identify proteolytic cleavage products after digestion with trypsin, a common protease that breaks down proteins.
  • Major cartilage proteoglycans, including aggrecan, biglycan, decorin, fibromodulin, and cartilage oligomeric matrix protein, were examined in this context.
  • The study identified previously known and novel cleavage sites, expanding the understanding of the degradation process.

Implications and Future Applications

  • The discovery of new neopeptides not only enhances our understanding of osteoarthritis but also provides a foundation for identifying biomarkers for the disease.
  • With this knowledge, scientists could potentially develop antibodies to specifically target these biomarkers, providing a new approach to the diagnosis and treatment of osteoarthritis.
  • The study, therefore, not only elucidates the basic biochemical processes involved in osteoarthritis but also opens the door for further research in veterinary medicine and potential applications in human medicine.

Cite This Article

APA
Peffers MJ, Thornton DJ, Clegg PD. (2015). Characterization of neopeptides in equine articular cartilage degradation. J Orthop Res, 34(1), 106-120. https://doi.org/10.1002/jor.22963

Publication

Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
NlmUniqueID: 8404726
Country: United States
Language: English
Volume: 34
Issue: 1
Pages: 106-120

Researcher Affiliations

Peffers, Mandy Jayne
  • Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Leahurst, Chester High Road, Neston, Wirral, CH64 7TE, UK.
Thornton, David James
  • Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK.
Clegg, Peter David
  • Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Leahurst, Chester High Road, Neston, Wirral, CH64 7TE, UK.

MeSH Terms

  • Animals
  • Biomarkers / metabolism
  • Cartilage, Articular / metabolism
  • Centrifugation, Density Gradient
  • Horses
  • Humans
  • Interleukin-1beta
  • Osteoarthritis / metabolism
  • Peptide Hydrolases / metabolism
  • Peptides / metabolism
  • Proteoglycans / metabolism
  • Recombinant Proteins

Grant Funding

  • 088785 / Wellcome Trust
  • MR/K006312/1 / Medical Research Council
  • WT088557MA / Wellcome Trust
  • Arthritis Research UK

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