Abstract
Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) lead to cartilage destruction, and the activation of NF‑κB is important in the proliferation of FLSs. Heparin is a glycosaminoglycan, which is widely used as an anticoagulant. In the present study, the effect of heparin on the tumor necrosis factor (TNF)‑α induced proliferation of FLSs was investigated. Western blot and polymerase chain reaction analyses were used to assess the expression levels of cytokines. The results revealed that TNF‑α induced the expression of interleukin (IL)‑6, IL‑8, TNF‑α and cyclin D1. Heparin inhibited the growth rate of the FLSs induced by TNF‑α. Heparin also decreased the TNF‑α‑induced mRNA and protein expression levels of IL‑6, IL‑8, TNF‑α and cyclin D1 in a dose‑dependent manner. Immunofluorescence analysis showed that the expression of cytoplasmic TNF‑α was significantly reduced by heparin treatment. Furthermore, the levels of p65 and inhibitor of nuclear factor (NF)‑κB phosphorylation were inhibited by heparin treatment, suggesting that heparin induced the inhibition of NF‑κB. In conclusion, the results of the present study revealed that heparin inhibited the TNF‑α‑induced proliferation, cytokine production, expression of cyclin D1 and activation of NF‑κB signaling in FLSs, indicating the therapeutic potential of heparin in the treatment of RA.