机构：[1]Shanghai University of Traditional Chinese Medicine, Shanghai, China[2]Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, China[3]Jiangsu CM Clinical Innovation Center of Degenerative Bone & Joint Disease, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China[4]Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China[5]University of Chinese Academy of Sciences, Beijing, China[6]Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou, Guangdong, China[7]Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China[8]Shanghai Huashen Institute of Microbes and Infectio ns, Shanghai, China.
Fibroblast-like synoviocytes (FLS) contribute to inflammation and joint damage in rheumatoid arthritis (RA). However, the regulatory mechanisms of FLS in relapse and remission RA remain unknown. Identifying FLS heterogeneity and their underlying pathogenic roles may lead to discovering novel disease-modifying antirheumatic drugs.Combining single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics, we sequenced six matched synovial tissue samples from three relapse RA patients and three patients in remission. We analyzed the differences in the transcriptomes of the FLS subsets between the relapse and remitted phases. We validated several key signaling pathways using qPCR and multiplex immunohistochemistry (HC). We further targeted the critical signals in vitro and in vivo using collage-induced arthritis (CIA) model in rats.Lining and sublining FLS subsets were identified using scRNA-seq. Differential analyses indicated that the fibroblast growth factor (FGF) pathway was highly activated in the lining FLS from relapse RA patients where mIHC confirmed the increased expression of FGF10. While the type I interferon pathway was also activated in the lining FLS, in vitro stimulation experiment suggested that it was independent of the FGF10 pathway. FGF10 knockdown by siRNA in FLS significantly reduced the expression of RANKL. Moreover, recombinant FGF10 protein enhanced bone erosion in the primary human-derived pannus cell culture, whereas the FGFR1 inhibitor attenuated this process. Finally, administering an FGFR1 inhibitor displayed a therapeutic effect in a CIA rat model.The FGF pathway is a critical signaling pathway in relapse RA. Targeted tissue-specific inhibition of FGF10/FGFR1 may provide new opportunities to treat patients with relapse RA.This article is protected by copyright. All rights reserved.
基金：
This study was supported by the National Key Research and Development Program of
China (No. 2021YFE0200600 to XMZ); the Strategic Priority Research Program (No.
XDPB0303 to XMZ), Chinese Academy of Sciences; Shanghai Municipal Science and
Technology Fund (No. 22490760100 to XMZ); Shanghai Municipal Science and
Technology Major Project (No. 2019SHZDZX02 and HS2021SHZX001 to XMZ); the
Science and Technology Commission of Shanghai Municipality Fund (21Y11921500,
22Y11923200, 22ZR1453000, 22ZR1453100); Shanghai Municipal Health
Commission Fund (No. 202140163, shslczdzk04801, ZY (2021-2023)-0201-06);
Foundation of Jiangsu CM Clinical Innovation Center of Degenerative Bone & Joint
Disease (Jiangsu science and education of traditional Chinese medicine (2021) No. 4);Shanghai University of Traditional Chinese Medicine Postgraduate Innovation and
Training Project (No. Y2021056).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|1 区医学
小类|1 区风湿病学
最新[2025]版：
大类|1 区医学
小类|1 区风湿病学
第一作者：
第一作者机构：[1]Shanghai University of Traditional Chinese Medicine, Shanghai, China[2]Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, China[3]Jiangsu CM Clinical Innovation Center of Degenerative Bone & Joint Disease, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China
共同第一作者：
通讯作者：
通讯机构：[2]Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, China[4]Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China[5]University of Chinese Academy of Sciences, Beijing, China[7]Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China[8]Shanghai Huashen Institute of Microbes and Infectio ns, Shanghai, China.[*1]1474 Yan'an West Road, Changning District, Shanghai 200052[*2]320 Yueyang Road, Xuhui District, Shanghai 200031
推荐引用方式(GB/T 7714)：
Meng Xiaohui,Chen Zechuan,Li Teng,et al.Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis[J].Arthritis & rheumatology (Hoboken, N.J.).2023,doi:10.1002/art.42674.
APA：
Meng Xiaohui,Chen Zechuan,Li Teng,Nie Zhixing,Han Haihui...&Xiao Lianbo.(2023).Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.),,
MLA：
Meng Xiaohui,et al."Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis".Arthritis & rheumatology (Hoboken, N.J.) .(2023)
医学