title: Ganglioside GM3 has an essential role in the pathogenesis and progression of rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA), a chronic systemic inflammatory disorder that principally attacks synovial joints, afflicts over 2 million people in the United States. Interleukin (IL)-17 is considered to be a master cytokine in chronic, destructive arthritis. Levels of the ganglioside GM3, one of the most primitive glycosphingolipids containing a sialic acid in the structure, are remarkably decreased in the synovium of patients with RA. Based on the increased cytokine secretions observed in in vitro experiments, GM3 might have an immunologic role. Here, to clarify the association between RA and GM3, we established a collagen-induced arthritis mouse model using the null mutation of the ganglioside GM3 synthase gene. GM3 deficiency exacerbated inflammatory arthritis in the mouse model of RA. In addition, disrupting GM3 induced T cell activation in vivo and promoted overproduction of the cytokines involved in RA. In contrast, the amount of the GM3 synthase gene transcript in the synovium was higher in patients with RA than in those with osteoarthritis. These findings indicate a crucial role for GM3 in the pathogenesis and progression of RA. Control of glycosphingolipids such as GM3 might therefore provide a novel therapeutic strategy for RA.
authors: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Yukinori
authors: Y
authors: Tsukuda
authors: Norimasa
authors: N
authors: Iwasaki
authors: Naoki
authors: N
authors: Seito
authors: Masashi
authors: M
authors: Kanayama
authors: Naoki
authors: N
authors: Fujitani
authors: Yasuro
authors: Y
authors: Shinohara
authors: Yasuhiko
authors: Y
authors: Kasahara
authors: Tomohiro
authors: T
authors: Onodera
authors: Koji
authors: K
authors: Suzuki
authors: Tsuyoshi
authors: T
authors: Asano
authors: Akio
authors: A
authors: Minami
authors: Tadashi
authors: T
authors: Yamashita
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000201:enzymology / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D053898:Biosynthetic Pathways / Q000187:drug effects; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005679:G(M3) Ganglioside / Q000378:metabolism*; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012799:Sialyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000906:Antibodies; D017252:CD3 Complex; D005679:G(M3) Ganglioside; D012333:RNA, Messenger; D012799:Sialyltransferases; C021343:haematoside synthetase