Rheumatoid arthritis chondrocytes produce increased levels of pro-inflammatory proteins.

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.