A human meniscus explant model for studying early events in osteoarthritis development by proteomics

Martin Rydén, Karin Lindblom, Aida Yifter-Lindgren, Aleksandra Turkiewicz, Anders Aspberg, Viveka Tillgren, Martin Englund, Patrik Önnerfjord

Research output: Contribution to journalArticlepeer-review

Abstract

Degenerative meniscus lesions have been associated with both osteoarthritis etiology and its progression. We, therefore, sought to establish a human meniscus ex vivo model to study the meniscal response to cytokine treatment using a proteomics approach. Lateral menisci were obtained from five knee-healthy donors. The meniscal body was cut into vertical slices and further divided into an inner (avascular) and outer region. Explants were either left untreated (controls) or stimulated with cytokines. Medium changes were conducted every 3 days up to Day 21 and liquid chromatography–mass spectrometry was performed at all the time points for the identification and quantification of proteins. Mixed-effect linear regression models were used for statistical analysis to estimate the effect of treatments versus control on protein abundance. Treatment by IL1ß increased release of cytokines such as interleukins, chemokines, and matrix metalloproteinases but a limited catabolic effect in healthy human menisci explants. Further, we observed an increased release of matrix proteins (collagens, integrins, prolargin, tenascin) in response to oncostatin M (OSM) + tumor necrosis factor (TNF) and TNF+interleukin-6 (IL6) + sIL6R treatments, and analysis of semitryptic peptides provided additional evidence of increased catabolic effects in response to these treatments. The induced activation of catabolic processes may play a role in osteoarthritis development.

Original languageEnglish
Pages (from-to)2765-2778
Number of pages14
JournalJournal of Orthopaedic Research
Volume41
Issue number12
Early online date2023 May 23
DOIs
Publication statusPublished - 2023

Bibliographical note

Funding Information:
This work was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement #771121), The Swedish Research Council, the ALF agreement between the Swedish government and the county, the Swedish Rheumatism Association, IngaBritt and Arne Lundberg's Research Foundation, the Alfred Österlund Foundation, the Olle Engkvist Foundation, the Greta & Johan Kock Foundation, The Foundation for Movement Disabilities in Skåne, the Anna‐Greta Crafoord and the Crafoord Foundations.

Publisher Copyright:
© 2023 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.

Subject classification (UKÄ)

  • Rheumatology and Autoimmunity

Free keywords

  • cytokines
  • explants
  • meniscus
  • osteoarthritis
  • proteomics

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