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Cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: A new biomarker for the early stages of osteoarthritis

BACKGROUND: Clinical tools to diagnose the early changes of osteoarthritis (OA) that occur in the articular cartilage are lacking. OBJECTIVES: We sought to identify and quantify a novel cartilage oligomeric matrix protein (COMP) neoepitope in the synovial fluid from the joints of healthy horses and...

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Autores principales: Skiöldebrand, E., Ekman, S., Mattsson Hultén, L., Svala, E., Björkman, K., Lindahl, A., Lundqvist, A., Önnerfjord, P., Sihlbom, C., Rüetschi, U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573946/
https://www.ncbi.nlm.nih.gov/pubmed/28097685
http://dx.doi.org/10.1111/evj.12666
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author Skiöldebrand, E.
Ekman, S.
Mattsson Hultén, L.
Svala, E.
Björkman, K.
Lindahl, A.
Lundqvist, A.
Önnerfjord, P.
Sihlbom, C.
Rüetschi, U.
author_facet Skiöldebrand, E.
Ekman, S.
Mattsson Hultén, L.
Svala, E.
Björkman, K.
Lindahl, A.
Lundqvist, A.
Önnerfjord, P.
Sihlbom, C.
Rüetschi, U.
author_sort Skiöldebrand, E.
collection PubMed
description BACKGROUND: Clinical tools to diagnose the early changes of osteoarthritis (OA) that occur in the articular cartilage are lacking. OBJECTIVES: We sought to identify and quantify a novel cartilage oligomeric matrix protein (COMP) neoepitope in the synovial fluid from the joints of healthy horses and those with different stages of OA. STUDY DESIGN: In vitro quantitative proteomics and assay development with application in synovial fluids samples obtained from biobanks of well‐characterised horses. METHODS: Articular cartilage explants were incubated with or without interleukin‐1β for 25 days. Media were analysed via quantitative proteomics. Synovial fluid was obtained from either normal joints (n = 15) or joints causing lameness (n = 17) or with structural OA lesions (n = 7) and analysed for concentrations of the COMP neoepitope using a custom‐developed inhibition enzyme‐linked immunosorbent assay (ELISA). Explants were immunostained with polyclonal antibodies against COMP and the COMP neoepitopes. RESULTS: Semitryptic COMP peptides were identified and quantified in cell culture media from cartilage explants. A rabbit polyclonal antibody was raised against the neoepitope of the N‐terminal portion of one COMP fragment (sequence SGPTHEGVC). An inhibition ELISA was developed to quantify the COMP neoepitope in synovial fluid. The mean concentration of the COMP neoepitope significantly increased in the synovial fluid from the joints responsible for acute lameness compared with normal joints and the joints of chronically lame horses and in joints with chronic structural OA. Immunolabelling for the COMP neoepitope revealed a pericellular staining in the interleukin‐1β‐stimulated explants. MAIN LIMITATIONS: The ELISA is based on polyclonal antisera rather than a monoclonal antibody. CONCLUSIONS: The increase in the COMP neoepitope in the synovial fluid from horses with acute lameness suggests that this neoepitope has the potential to be a unique candidate biomarker for the early molecular changes in articular cartilage associated with OA.
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spelling pubmed-55739462017-09-15 Cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: A new biomarker for the early stages of osteoarthritis Skiöldebrand, E. Ekman, S. Mattsson Hultén, L. Svala, E. Björkman, K. Lindahl, A. Lundqvist, A. Önnerfjord, P. Sihlbom, C. Rüetschi, U. Equine Vet J Experimental and Basic Research Studies BACKGROUND: Clinical tools to diagnose the early changes of osteoarthritis (OA) that occur in the articular cartilage are lacking. OBJECTIVES: We sought to identify and quantify a novel cartilage oligomeric matrix protein (COMP) neoepitope in the synovial fluid from the joints of healthy horses and those with different stages of OA. STUDY DESIGN: In vitro quantitative proteomics and assay development with application in synovial fluids samples obtained from biobanks of well‐characterised horses. METHODS: Articular cartilage explants were incubated with or without interleukin‐1β for 25 days. Media were analysed via quantitative proteomics. Synovial fluid was obtained from either normal joints (n = 15) or joints causing lameness (n = 17) or with structural OA lesions (n = 7) and analysed for concentrations of the COMP neoepitope using a custom‐developed inhibition enzyme‐linked immunosorbent assay (ELISA). Explants were immunostained with polyclonal antibodies against COMP and the COMP neoepitopes. RESULTS: Semitryptic COMP peptides were identified and quantified in cell culture media from cartilage explants. A rabbit polyclonal antibody was raised against the neoepitope of the N‐terminal portion of one COMP fragment (sequence SGPTHEGVC). An inhibition ELISA was developed to quantify the COMP neoepitope in synovial fluid. The mean concentration of the COMP neoepitope significantly increased in the synovial fluid from the joints responsible for acute lameness compared with normal joints and the joints of chronically lame horses and in joints with chronic structural OA. Immunolabelling for the COMP neoepitope revealed a pericellular staining in the interleukin‐1β‐stimulated explants. MAIN LIMITATIONS: The ELISA is based on polyclonal antisera rather than a monoclonal antibody. CONCLUSIONS: The increase in the COMP neoepitope in the synovial fluid from horses with acute lameness suggests that this neoepitope has the potential to be a unique candidate biomarker for the early molecular changes in articular cartilage associated with OA. John Wiley and Sons Inc. 2017-02-28 2017-09 /pmc/articles/PMC5573946/ /pubmed/28097685 http://dx.doi.org/10.1111/evj.12666 Text en © 2017 The Authors Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Experimental and Basic Research Studies
Skiöldebrand, E.
Ekman, S.
Mattsson Hultén, L.
Svala, E.
Björkman, K.
Lindahl, A.
Lundqvist, A.
Önnerfjord, P.
Sihlbom, C.
Rüetschi, U.
Cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: A new biomarker for the early stages of osteoarthritis
title Cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: A new biomarker for the early stages of osteoarthritis
title_full Cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: A new biomarker for the early stages of osteoarthritis
title_fullStr Cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: A new biomarker for the early stages of osteoarthritis
title_full_unstemmed Cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: A new biomarker for the early stages of osteoarthritis
title_short Cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: A new biomarker for the early stages of osteoarthritis
title_sort cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: a new biomarker for the early stages of osteoarthritis
topic Experimental and Basic Research Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573946/
https://www.ncbi.nlm.nih.gov/pubmed/28097685
http://dx.doi.org/10.1111/evj.12666
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