%0 Journal Article
%T FTO-mediated RNA m6A methylation regulates synovial aggression and inflammation in rheumatoid arthritis.
%A Li R
%A Kuang Y
%A Niu Y
%A Zhang S
%A Chen S
%A Su F
%A Wang J
%A Lin S
%A Liu D
%A Shen C
%A Liang L
%A Zheng SG
%A Jie L
%A Xiao Y
%A Xu H
%J Biochim Biophys Acta Mol Basis Dis
%V 1870
%N 7
%D 2024 10 16
%M 39025373
%F 6.633
%R 10.1016/j.bbadis.2024.167341
%X Fibroblast-like synoviocytes (FLS) plays an important role in synovial inflammation and joint damage in rheumatoid arthritis (RA). As the most abundant mRNA modification, N6-methyladenosine (m6A) is involved in the development of various diseases; however, its role in RA remains to be defined. In this study, we reported the elevated expression of the m6A demethylase fat mass and obesity-associated protein (FTO) in FLS and synovium from RA patients. Functionally, FTO knockdown or treatment with FB23-2, an inhibitor of the mRNA m6A demethylase FTO, inhibited the migration, invasion and inflammatory response of RA FLS, however, FTO-overexpressed RA FLS exhibited increased migration, invasion and inflammatory response. We further demonstrated that FTO promoted ADAMTS15 mRNA stability in an m6A-IGF2BP1 dependent manner. Notably, the severity of arthritis was significantly reduced in CIA mice with FB23-2 administration or CIA rats with intra-articular injection of FTO shRNA. Our results illustrate the contribution of FTO-mediated m6A modification to joint damage and inflammation in RA and suggest that FTO might be a potential therapeutic target in RA.