{Reference Type}: Journal Article
{Title}: γ-Secretase inhibitors suppress IL-20-mediated osteoclastogenesis via Notch signalling and are affected by Notch2 in vitro.
{Author}: Yang B;Fu C;Wu Y;Liu Y;Zhang Z;Chen X;Wu D;Gan Z;Chen Z;Cao Y;Yang B;Fu C;Wu Y;Liu Y;Zhang Z;Chen X;Wu D;Gan Z;Chen Z;Cao Y;
{Journal}: Scand J Immunol
{Volume}: 96
{Issue}: 2
{Year}: Aug 2022
{Factor}: 3.889
{DOI}: 10.1111/sji.13169
{Abstract}: 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.