%0 Journal Article
%T γ-Secretase inhibitors suppress IL-20-mediated osteoclastogenesis via Notch signalling and are affected by Notch2 in vitro.
%A Yang B
%A Fu C
%A Wu Y
%A Liu Y
%A Zhang Z
%A Chen X
%A Wu D
%A Gan Z
%A Chen Z
%A Cao Y
%A Yang B
%A Fu C
%A Wu Y
%A Liu Y
%A Zhang Z
%A Chen X
%A Wu D
%A Gan Z
%A Chen Z
%A Cao Y
%J Scand J Immunol
%V 96
%N 2
%D Aug 2022
%M 35384009
%F 3.889
%R 10.1111/sji.13169
%X Rheumatoid arthritis (RA) is a chronic immune disease involving the small joints, which often causes irreversible damage. In recent years, elevated interleukin 20 (IL-20) has been observed in synovial fluid, while IL-20 receptor overexpression has been observed in synovial cells. IL-20 is a pleiotropic cytokine that participates in various immune diseases. Further understanding of the relationship between IL-20 and RA can help to identify a potential clinical treatment for RA. This study demonstrated that IL-20 can regulate osteoclast differentiation and function in a dose-dependent manner, while influencing the expression of Notch signalling. Quantitative reverse transcription polymerase chain reaction and western blotting showed that γ-secretase-inhibiting drugs can reverse the effects of IL-20. The effects of Notch2 on IL-20-induced osteoclastogenesis were investigated by immunofluorescence and Notch2 gene silencing via transfection of small interfering RNA; the results showed that Notch2 obviously affected the expression levels of the key protein NFATc1 and downstream osteoclastic proteins. In conclusion, we found that IL-20 regulated the osteoclastogenesis in a dose-dependent manner via Notch signalling, primarily by means of Notch2 activity. This study may help to find new targets for RA treatment.