Inflammatory Treatment Used to Mimic Osteoarthritis and Patients' Synovial Fluid Have Divergent Molecular Impact on Chondrocytes In Vitro

Osteoarthritis (OA) is a chronic disease characterized by joint tissue disruption and inflammation with a paucity of therapeutic options. Chondrocyte in vitro models are commonly used as the first step in evaluating new approaches and rely on the stimulation of an OA-like phenotype with inflammation often the method of choice. Inflammatory priming is frequently based on cytokines used at concentrations very far from the reality in the patients' synovial fluid (SF). The aim of this work was to compare the transcriptional response of chondrocytes to different inflammatory conditions: the high levels of IL1 beta that are used for standardized inflammation protocols, OA-SF, IL1 beta, IL6 and IFN gamma at SF-like concentrations both individually and simultaneously to mimic a simplified in vitro SF. Both high IL1 beta and OA-SF strongly influenced chondrocytes, while SF-like concentrations of cytokines gave weak (IL1 beta alone or in combination) or no (IL6 and IFN gamma alone) outcomes. Chondrocytes under the two most powerful polarizing conditions had a clearly distinct fingerprint, with only a shared albeit molecularly divergent effect on ECM stability, with IL1 beta mainly acting on ECM degrading enzymes and OA-SF accounting for a higher turnover in favor of fibrous collagens. Moreover, OA-SF did not induce the inflammatory response observed with IL1 beta. In conclusion, although partially similar in the endpoint phenotype, this work intends to encourage reflection on the robustness of inflammation-based in vitro OA models for molecular studies on chondrocytes.

Automated summary

Osteoarthritis (OA) is a chronic disease with limited therapeutic options. In vitro models using chondrocytes are commonly used to evaluate new approaches, but the inflammation-based models may not accurately represent the real inflammatory conditions in patients. This study aimed to compare the transcriptional response of chondrocytes to different inflammatory conditions.