FABP4 secreted by M1-polarized macrophages promotes synovitis and angiogenesis to exacerbate rheumatoid arthritis  

作　　者：Dong Guo Chuangxin Lin Yuheng Lu Hong Guan Weizhong Qi Hongbo Zhang Yan Shao Chun Zeng Rongkai Zhang Haiyan Zhang Xiaochun Bai Daozhang Cai 

机构地区：[1]Department of Joint Surgery,Center for Orthopedic Surgery,The Third Affiliated Hospital of Southern Medical University,Guangzhou,China [2]Department of Orthopedics,Orthopedic Hospital of Guangdong Province,Academy of Orthopedics,Guangdong Province,The Third Affiliated Hospital of Southern Medical University,Guangzhou,China [3]The Third School of Clinical Medicine,Southern Medical University,Guangzhou,China [4]Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases,Guangzhou,China [5]Department of Orthopedic Surgery,Shantou Central Hospital,Affiliated Shantou Hospital of Sun Yat-sen University,Shantou,China [6]State Key Laboratory of Organ Failure Research,Department of Cell Biology,Southern Medical University School of Basic Medical Sciences,Guangzhou,China

出　　处：《Bone Research》2022年第4期726-740,共15页骨研究（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(Grant Nos.81772406,81974341,81991511,81625015,and 81902268);the Natural Science Foundation of Guangdong Province(2020A1515010207 and 2022A1515010431);the China Postdoctoral Science Foundation(2019M663264 and 2019TQ0385).

摘　　要：Increasing evidence shows that adipokines play a vital role in the development of rheumatoid arthritis(RA).Fatty acid-binding protein 4(FABP4),a novel adipokine that regulates inflammation and angiogenesis,has been extensively studied in a variety of organs and diseases.However,the effect of FABP4 on RA remains unclear.Here,we found that FABP4 expression was upregulated in synovial M1-polarized macrophages in RA.The increase in FABP4 promoted synovitis,angiogenesis,and cartilage degradation to exacerbate RA progression in vivo and in vitro,whereas BMS309403(a FABP4 inhibitor)and anagliptin(dipeptidyl peptidase 4 inhibitor)inhibited FABP4 expression in serum and synovial M1-polarized macrophages in mice to alleviate RA progression.Further studies showed that constitutive activation of mammalian target of rapamycin complex 1(mTORC1)by TSC1 deletion specifically in the myeloid lineage regulated FABP4 expression in macrophages to exacerbate RA progression in mice.In contrast,inhibition of mTORC1 by ras homolog enriched in brain(Rheb1)disruption specifically in the myeloid lineage reduced FABP4 expression in macrophages to attenuate RA development in mice.Our findings established an essential role of FABP4 that is secreted by M1-polarized macrophages in synovitis,angiogenesis,and cartilage degradation in RA.BMS309403 and anagliptin inhibited FABP4 expression in synovial M1-polarized macrophages to alleviate RA development.Hence,FABP4 may represent a potential target for RA therapy.

关 键 词：ANGIOGENESIS inhibited SYNOVITIS 

分 类 号：R593.22[医药卫生—内科学]