Chondrocytes from Osteoarthritis Patients Adopt Distinct Phenotypes in Response to Central T<sub>H</sub>1/T<sub>H</sub>2/T<sub>H</sub>17 Cytokines
Chronic low-grade inflammation plays a central role in the pathogenesis of osteoarthritis (OA), and several pro- and anti-inflammatory cytokines have been implicated to mediate and regulate this process. Out of these cytokines, particularly IFNγ, IL-1β, IL-4 and IL-17 are associated with different p...
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9463 |
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| author | Antti Pemmari Tiina Leppänen Mari Hämäläinen Teemu Moilanen Eeva Moilanen |
| author_facet | Antti Pemmari Tiina Leppänen Mari Hämäläinen Teemu Moilanen Eeva Moilanen |
| author_sort | Antti Pemmari |
| collection | DOAJ |
| description | Chronic low-grade inflammation plays a central role in the pathogenesis of osteoarthritis (OA), and several pro- and anti-inflammatory cytokines have been implicated to mediate and regulate this process. Out of these cytokines, particularly IFNγ, IL-1β, IL-4 and IL-17 are associated with different phenotypes of T helper (T<sub>H</sub>) cells and macrophages, both examples of cells known for great phenotypic and functional heterogeneity. Chondrocytes also display various phenotypic changes during the course of arthritis. We set out to study the hypothesis of whether chondrocytes might adopt polarized phenotypes analogous to T<sub>H</sub> cells and macrophages. We studied the effects of IFNγ, IL-1β, IL-4 and IL-17 on gene expression in OA chondrocytes with RNA-Seq. Chondrocytes were harvested from the cartilage of OA patients undergoing knee replacement surgery and then cultured with or without the cytokines for 24 h. Total RNA was isolated and sequenced, and GO (Gene Ontology) functional analysis was performed. We also separately investigated genes linked to OA in recent genome wide expression analysis (GWEA) studies. The expression of more than 2800 genes was significantly altered in chondrocytes treated with IL-1β [in the C(IL-1β) phenotype] with a fold change (FC) > 2.5 in either direction. These included a large number of genes associated with inflammation, cartilage degradation and attenuation of metabolic signaling. The profile of genes differentially affected by IFNγ (the C(IFNγ) phenotype) was relatively distinct from that of the C(IL-1β) phenotype and included several genes associated with antigen processing and presentation. The IL-17-induced C(IL-17) phenotype was characterized by the induction of a more limited set of proinflammatory factors compared to C(IL-1β) cells. The C(IL-4) phenotype induced by IL-4 displayed a differential expression of a rather small set of genes compared with control, primarily those associated with TGFβ signaling and the regulation of inflammation. In conclusion, our results show that OA chondrocytes can adopt diverse phenotypes partly analogously to T<sub>H</sub> cells and macrophages. This phenotypic plasticity may play a role in the pathogenesis of arthritis and open new therapeutic avenues for the development of disease-modifying treatments for (osteo)arthritis. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:10:41Z |
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| spelling | doaj.art-5380469ffea8415eaffb1b75d57d87052023-11-22T10:44:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217946310.3390/ijms22179463Chondrocytes from Osteoarthritis Patients Adopt Distinct Phenotypes in Response to Central T<sub>H</sub>1/T<sub>H</sub>2/T<sub>H</sub>17 CytokinesAntti Pemmari0Tiina Leppänen1Mari Hämäläinen2Teemu Moilanen3Eeva Moilanen4The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, University of Tampere and Tampere University Hospital, 33100 Tampere, FinlandThe Immunopharmacology Research Group, Faculty of Medicine and Health Technology, University of Tampere and Tampere University Hospital, 33100 Tampere, FinlandThe Immunopharmacology Research Group, Faculty of Medicine and Health Technology, University of Tampere and Tampere University Hospital, 33100 Tampere, FinlandCoxa Hospital for Joint Replacement, 33520 Tampere, FinlandThe Immunopharmacology Research Group, Faculty of Medicine and Health Technology, University of Tampere and Tampere University Hospital, 33100 Tampere, FinlandChronic low-grade inflammation plays a central role in the pathogenesis of osteoarthritis (OA), and several pro- and anti-inflammatory cytokines have been implicated to mediate and regulate this process. Out of these cytokines, particularly IFNγ, IL-1β, IL-4 and IL-17 are associated with different phenotypes of T helper (T<sub>H</sub>) cells and macrophages, both examples of cells known for great phenotypic and functional heterogeneity. Chondrocytes also display various phenotypic changes during the course of arthritis. We set out to study the hypothesis of whether chondrocytes might adopt polarized phenotypes analogous to T<sub>H</sub> cells and macrophages. We studied the effects of IFNγ, IL-1β, IL-4 and IL-17 on gene expression in OA chondrocytes with RNA-Seq. Chondrocytes were harvested from the cartilage of OA patients undergoing knee replacement surgery and then cultured with or without the cytokines for 24 h. Total RNA was isolated and sequenced, and GO (Gene Ontology) functional analysis was performed. We also separately investigated genes linked to OA in recent genome wide expression analysis (GWEA) studies. The expression of more than 2800 genes was significantly altered in chondrocytes treated with IL-1β [in the C(IL-1β) phenotype] with a fold change (FC) > 2.5 in either direction. These included a large number of genes associated with inflammation, cartilage degradation and attenuation of metabolic signaling. The profile of genes differentially affected by IFNγ (the C(IFNγ) phenotype) was relatively distinct from that of the C(IL-1β) phenotype and included several genes associated with antigen processing and presentation. The IL-17-induced C(IL-17) phenotype was characterized by the induction of a more limited set of proinflammatory factors compared to C(IL-1β) cells. The C(IL-4) phenotype induced by IL-4 displayed a differential expression of a rather small set of genes compared with control, primarily those associated with TGFβ signaling and the regulation of inflammation. In conclusion, our results show that OA chondrocytes can adopt diverse phenotypes partly analogously to T<sub>H</sub> cells and macrophages. This phenotypic plasticity may play a role in the pathogenesis of arthritis and open new therapeutic avenues for the development of disease-modifying treatments for (osteo)arthritis.https://www.mdpi.com/1422-0067/22/17/9463chondrocyteIL-1βIFNγ, IL-17IL-4RNA-Seq |
| spellingShingle | Antti Pemmari Tiina Leppänen Mari Hämäläinen Teemu Moilanen Eeva Moilanen Chondrocytes from Osteoarthritis Patients Adopt Distinct Phenotypes in Response to Central T<sub>H</sub>1/T<sub>H</sub>2/T<sub>H</sub>17 Cytokines International Journal of Molecular Sciences chondrocyte IL-1β IFNγ, IL-17 IL-4 RNA-Seq |
| title | Chondrocytes from Osteoarthritis Patients Adopt Distinct Phenotypes in Response to Central T<sub>H</sub>1/T<sub>H</sub>2/T<sub>H</sub>17 Cytokines |
| title_full | Chondrocytes from Osteoarthritis Patients Adopt Distinct Phenotypes in Response to Central T<sub>H</sub>1/T<sub>H</sub>2/T<sub>H</sub>17 Cytokines |
| title_fullStr | Chondrocytes from Osteoarthritis Patients Adopt Distinct Phenotypes in Response to Central T<sub>H</sub>1/T<sub>H</sub>2/T<sub>H</sub>17 Cytokines |
| title_full_unstemmed | Chondrocytes from Osteoarthritis Patients Adopt Distinct Phenotypes in Response to Central T<sub>H</sub>1/T<sub>H</sub>2/T<sub>H</sub>17 Cytokines |
| title_short | Chondrocytes from Osteoarthritis Patients Adopt Distinct Phenotypes in Response to Central T<sub>H</sub>1/T<sub>H</sub>2/T<sub>H</sub>17 Cytokines |
| title_sort | chondrocytes from osteoarthritis patients adopt distinct phenotypes in response to central t sub h sub 1 t sub h sub 2 t sub h sub 17 cytokines |
| topic | chondrocyte IL-1β IFNγ, IL-17 IL-4 RNA-Seq |
| url | https://www.mdpi.com/1422-0067/22/17/9463 |
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