Identification of tissue-dependent proteins in knee OA synovial fluid

U.T. Timur, H. Jahr, J. Anderson, D.C. Green, P.J. Emans, A. Smagul, L.W. van Rhijn, M.J. Peffers, T.J.M. Welting*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective: For many proteins from osteoarthritic synovial fluid, their intra-articular tissue of origin remains unknown. In this study we performed comparative proteomics to identify osteoarthritis-specific and joint tissue-dependent secreted proteins that may serve as candidates for osteoarthritis biomarker development on a tissue-specific basis.Design: Protein secretomes of cartilage, synovium, Hoffa's fat pad and meniscus from knee osteoarthritis patients were determined using liquid chromatography tandem mass spectrometry, followed by label-free quantification. Validation of tissue-dependent protein species was conducted by ELISA on independent samples. Differential proteomes of osteoarthritic and non-osteoarthritic knee synovial fluids were obtained via similar proteomics approach, followed by ELISA validation.Results: Proteomics revealed 64 proteins highly secreted from cartilage, 94 from synovium, 37 from Hoffa's fat pad and 21 from meniscus. Proteomic analyses of osteoarthritic vs non-osteoarthritic knee synovial fluid revealed 70 proteins with a relatively higher abundance and 264 proteins with a relatively lower abundance in osteoarthritic synovial fluid. Of the 70 higher abundance proteins, 23 were amongst the most highly expressed in the secretomes of a specific intra-articular tissue measured. Tissue-dependent release was validated for SLPI, C8, CLU, FN1, RARRES2, MATN3, MMP3 and TNC. Abundance in synovial fluid of tissue-dependent proteins was validated for IGF2, AHSG, FN1, CFB, KNG and C8.Conclusions: We identified proteins with a tissue-dependent release from intra-articular human knee OA tissues. A number of these proteins also had an osteoarthritis-specific abundance in knee synovial fluid. These proteins may serve as novel candidates for osteoarthritis biomarker development on a tissue-specific basis. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
Original languageEnglish
Pages (from-to)124-133
Number of pages10
JournalOsteoarthritis and Cartilage
Issue number1
Publication statusPublished - 1 Jan 2021


  • biomarker
  • joint
  • knee joint
  • osteoarthritis
  • proteomics
  • stage
  • synovial fluid
  • tissue-dependent
  • Biomarker
  • Synovial fluid
  • Knee joint
  • Proteomics
  • Tissue-dependent
  • Osteoarthritis

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