Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ragni, Enrico, De Luca, Paola, Valli, Federico, Zagra, Luigi, de Girolamo, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916904/
https://www.ncbi.nlm.nih.gov/pubmed/36768948
http://dx.doi.org/10.3390/ijms24032625
_version_ 1784886239790366720
author Ragni, Enrico
De Luca, Paola
Valli, Federico
Zagra, Luigi
de Girolamo, Laura
author_facet Ragni, Enrico
De Luca, Paola
Valli, Federico
Zagra, Luigi
de Girolamo, Laura
author_sort Ragni, Enrico
collection PubMed
description 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 IL1β that are used for standardized inflammation protocols, OA-SF, IL1β, IL6 and IFNγ at SF-like concentrations both individually and simultaneously to mimic a simplified “in vitro” SF. Both high IL1β and OA-SF strongly influenced chondrocytes, while SF-like concentrations of cytokines gave weak (IL1β alone or in combination) or no (IL6 and IFNγ 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 IL1β 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 IL1β. 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.
format Online
Article
Text
id pubmed-9916904
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-99169042023-02-11 Inflammatory Treatment Used to Mimic Osteoarthritis and Patients’ Synovial Fluid Have Divergent Molecular Impact on Chondrocytes In Vitro Ragni, Enrico De Luca, Paola Valli, Federico Zagra, Luigi de Girolamo, Laura Int J Mol Sci Article 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 IL1β that are used for standardized inflammation protocols, OA-SF, IL1β, IL6 and IFNγ at SF-like concentrations both individually and simultaneously to mimic a simplified “in vitro” SF. Both high IL1β and OA-SF strongly influenced chondrocytes, while SF-like concentrations of cytokines gave weak (IL1β alone or in combination) or no (IL6 and IFNγ 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 IL1β 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 IL1β. 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. MDPI 2023-01-30 /pmc/articles/PMC9916904/ /pubmed/36768948 http://dx.doi.org/10.3390/ijms24032625 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ragni, Enrico
De Luca, Paola
Valli, Federico
Zagra, Luigi
de Girolamo, Laura
Inflammatory Treatment Used to Mimic Osteoarthritis and Patients’ Synovial Fluid Have Divergent Molecular Impact on Chondrocytes In Vitro
title Inflammatory Treatment Used to Mimic Osteoarthritis and Patients’ Synovial Fluid Have Divergent Molecular Impact on Chondrocytes In Vitro
title_full Inflammatory Treatment Used to Mimic Osteoarthritis and Patients’ Synovial Fluid Have Divergent Molecular Impact on Chondrocytes In Vitro
title_fullStr Inflammatory Treatment Used to Mimic Osteoarthritis and Patients’ Synovial Fluid Have Divergent Molecular Impact on Chondrocytes In Vitro
title_full_unstemmed Inflammatory Treatment Used to Mimic Osteoarthritis and Patients’ Synovial Fluid Have Divergent Molecular Impact on Chondrocytes In Vitro
title_short Inflammatory Treatment Used to Mimic Osteoarthritis and Patients’ Synovial Fluid Have Divergent Molecular Impact on Chondrocytes In Vitro
title_sort inflammatory treatment used to mimic osteoarthritis and patients’ synovial fluid have divergent molecular impact on chondrocytes in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916904/
https://www.ncbi.nlm.nih.gov/pubmed/36768948
http://dx.doi.org/10.3390/ijms24032625
work_keys_str_mv AT ragnienrico inflammatorytreatmentusedtomimicosteoarthritisandpatientssynovialfluidhavedivergentmolecularimpactonchondrocytesinvitro
AT delucapaola inflammatorytreatmentusedtomimicosteoarthritisandpatientssynovialfluidhavedivergentmolecularimpactonchondrocytesinvitro
AT vallifederico inflammatorytreatmentusedtomimicosteoarthritisandpatientssynovialfluidhavedivergentmolecularimpactonchondrocytesinvitro
AT zagraluigi inflammatorytreatmentusedtomimicosteoarthritisandpatientssynovialfluidhavedivergentmolecularimpactonchondrocytesinvitro
AT degirolamolaura inflammatorytreatmentusedtomimicosteoarthritisandpatientssynovialfluidhavedivergentmolecularimpactonchondrocytesinvitro