Synovitis biomarkers: ex vivo characterization of three biomarkers for identification of inflammatory osteoarthritis

Abstract

Objective: Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium.

Methods: Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in the conditioned medium.

Results: TNFα significantly increased C1M up to seven-fold (p = 0.0002), C3M up to 24-fold (p = 0.0011), and acMMP3 up to 14-fold (p < 0.0001) in SMEs. IL-1β also significantly increased C1M up to five-fold (p = 0.00094), C3M four-fold (p = 0.007), and acMMP3 18-fold (p < 0.0001) in SMEs.

Conclusion: The biomarkers C1M, C3M, and acMMP-3 were synovitis biomarkers ex vivo and provide a translational tool together with the SME model.

• Neo-epitope biomarkers
• personalized medicine
• synovial membrane

Declaration of interest

Anne-Christine Bay-Jensen and Morten Karsdal are full-time employees and shareholders in Nordic Bioscience. Anne Sofie Siebuhr is full-time employee of Nordic Bioscience and Christoph Ladel is full-time employee of Merck Serono, whereas Cecilie Kjelgaard-Petersen and Thorbjørn Christiansen report no declarations of interest. The authors would like to acknowledge The Danish Research Foundation for funding Nordic Bioscience and the D-Board consortium for supporting this work. The D-Board project has received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under Grant agreement no. 305815.

Author contributions

CFKP, ACBJ, CL, ASS and MK have planned and designed the experiment. CFKP conducted the experiment and measured the biomarkers. TC was responsible for providing the human synovial membranes. All authors were involved with data analysis, scientific discussion and interpretation of the data. Additionally, all authors were involved with drafting the manuscript, approving the manuscript prior to submission and have agreed to be accountable for all published data.