Rheumatoid arthritis chondrocytes produce increased levels of pro-inflammatory proteins

Karin Önnheim; Shan Huang; Alexander Strid Holmertz; Sofia Andersson; Erik Lönnblom; Charlotte Jonsson; Rikard Holmdahl; Inger Gjertsson

doi:10.1016/j.ocarto.2022.100235

Rheumatoid arthritis chondrocytes produce increased levels of pro-inflammatory proteins

Osteoarthr Cartil Open. 2022 Jan 21;4(1):100235. doi: 10.1016/j.ocarto.2022.100235. eCollection 2022 Mar.

Authors

Karin Önnheim¹, Shan Huang¹, Alexander Strid Holmertz¹, Sofia Andersson¹, Erik Lönnblom², Charlotte Jonsson¹, Rikard Holmdahl², Inger Gjertsson¹

Affiliations

¹ Dep of Rheumatology and Inflammation Research, Institute of Medicine, Gothenburg University, Sweden.
² Medical Inflammation Research, Dept of Medical Biochemistry and Biophysics, the Karolinska Institute, Stockholm, Sweden.

Abstract

Objective: To investigate whether articular chondrocytes from rheumatoid arthritis (RA) patients have acquired a proinflammatory phenotype.

Method: Articular cartilage explants from RA patients and healthy controls (HC) were cultured with or without interleukin (IL)-1β for two weeks. Protein levels of cytokines and metalloproteinases (MMPs) in the supernatant were measured by LUMINEX, mRNA with qPCR and nitrogen oxide (NO) levels with Griess assay.

Results: Within 24 h after culture, cartilage explants from RA spontaneously produced MMP-1 and MMP-13, and matrix components (aggrecan and collagen type IV) were released. In addition, the RA explants released higher levels of tumor necrosis factor, interferon-γ, IL-33, IL-18, vascular endothelial growth factor-A, IL-6 but not IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as compared with HC. During two weeks of incubation the higher levels did not diminish. IL-1β stimulation further increased the levels of IL-6, IL-8 and GM-CSF, mainly in RA explants, and induced increased levels of NO in the supernatant from both HC and RA explants, as a result of chondrocyte activation.

Conclusions: RA chondrocytes are activated with a proinflammatory profile involving the production of cytokines as well as MMP-1 and MMP-13, that can lead to release of matrix molecules after activation, which suggests that the chondrocytes have a proinflammatory phenotype and thereby an active role in the pathogenesis.

Keywords: Chondrocyte; Cytokine; Rheumatoid arthritis.