Abstract
To investigate the crosstalk between cartilage and fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), we adopted an in vitro coculture system model of collagen-induced arthritis (CIA) cartilage and CIA FLS monolayer. CIA rat samples of the synovium and femur head were collected for isolation of FLS and coculture system. Cartilages were treated with vehicle (Ctrl group), 10 ng/mL interleukin- (IL-) 1α (IL-1α group), and 10 ng/mL IL-1α plus 10 μM dexamethasone (Dex group) for 3 days before coculture with FLS for further 2 days. After the coculture, FLS were collected to determine the influences of articular cartilage on synoviocytes. Whether the CypB-CD147 signaling pathway is involved in the interactions between cartilage and FLS is assayed. Results showed that IL-1α-stimulated CIA cartilage promoted the proliferation and reduced the apoptosis of FLS. Increased inflammatory cytokines and decreased p57 expression were found in cocultured FLS stimulated by IL-1α-challenged CIA cartilage. Upregulation of NF-κB and I-κB kinase β (IKK-β) and downregulation of the inhibitor of NF-κBα (I-κBα) protein were observed in cocultured FLS. After coculture, significant increases in the expression of cyclophilin B (CypB) and CD147 were observed in CIA cartilage and FLS, respectively. Furthermore, results of immunofluorescence staining showed that the anti-CD147 antibody significantly suppressed p65 nuclear translocation in cocultured FLS stimulated by IL-1α-challenged CIA cartilage. In conclusion, inflammatory effects in the cartilage-FLS coculture system are associated with the CypB-CD147 mediating NF-κB pathway which may further enhance the inflammation in RA.
Highlights
Rheumatoid arthritis (RA), a chronic destructive articular synovial inflammatory disease, is featured by articular cartilage degradation and progressive bone erosion caused by synovial compartment inflammation
Treatment with Dex significantly downregulated the IL-1α-induced expression of inflammatory factors, Matrix metalloproteinases (MMPs) and cyclophilin B (CypB), in collagen-induced arthritis (CIA) cartilage
CIA cartilage will be used in the coculture system with CIA fibroblast-like synoviocytes (FLS) and Dex as the positive control drug to detect the crosstalk between cartilage and FLS
Summary
Rheumatoid arthritis (RA), a chronic destructive articular synovial inflammatory disease, is featured by articular cartilage degradation and progressive bone erosion caused by synovial compartment inflammation. The proliferating mass of fibroblast-like synoviocytes (FLS) locally invades the articular cartilage and bones and eventually destroys the whole joint. It causes excessive morbidity, mortality, and enormous socioeconomic burdens with an estimated prevalence of 0.5%-1% [1, 2]. Synovium-derived inflammatory factors, such as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6, correlate with inflammation-associated cartilage damage by upregulating matrix degradation enzymes [6, 7]. Matrix metalloproteinases (MMPs), induced by IL-1, TNF-α, and IL-17, exert an implicit role in the cartilage destruction process [8]. We intend to investigate the influences of articular cartilage on FLS functions and the interplay between them
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