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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)2765-2778
Antal sidor14
TidskriftJournal of Orthopaedic Research
Volym41
Nummer12
Tidigt onlinedatum2023 maj 23
DOI
StatusPublished - 2023

Bibliografisk information

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

Ämnesklassifikation (UKÄ)

  • Reumatologi och inflammation

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