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

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.

Automated summary

Degenerative meniscus lesions have been associated with both osteoarthritis etiology and its progression. In this study, a human meniscus ex vivo model was established to study the meniscal response to cytokine treatment using proteomics. The results showed that IL1β treatment increased the release of cytokines, while OSM+TNF and TNF+IL6+sIL6R treatments induced catabolic effects, which may contribute to the development of osteoarthritis.