title: Adiponectin exacerbates collagen-induced arthritis via enhancing Th17 response and prompting RANKL expression.
abstract: We previously reported adiponectin (AD) is highly expressed in the inflamed synovial joint tissue and correlates closely with progressive bone erosion in Rheumatoid arthritis (RA) patients. Here, we investigate the role of adiponectin in regulating Th17 response and the expression of receptor activator of nuclear factor-κB ligand (RANKL) in mice with CIA mice by intraarticularly injection of adiponectin into knee joints on day 17, day 20 and day 23 post first collagen immunization. The increased adiponectin expression was found in inflamed joint tissue of collagen-induced arthritis (CIA) mice. Adiponectin injection resulted in an earlier onset of arthritis, an aggravated arthritic progression, more severe synovial hyperplasia, bone erosion and osteoporosis in CIA mice. CD4(+)IL-17(+) Th17 cells, IL-17 mRNA and RANKL mRNA expression were markedly increased in the joint tissue of adiponectin treated CIA mice. Moreover, adiponectin treatment markedly enhanced Th17 cell generation from naive CD4(+) T cells in vitro, which accompanied by the high expression of Th17 transcription factor ROR-γt, and Th17 cytokine genes included IL-22 and IL-23. This study reveals a novel effect of adiponectin in exacerbating CIA progression by enhancing Th17 cell response and RANKL expression.
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: 1] Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China. [2] Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China.
authors.forename: Na
authors.initials: N
authors.lastname: Lin
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China.
authors.forename: Minhui
authors.initials: M
authors.lastname: Hua
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ningli
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China.
authors.forename: Miaojia
authors.initials: M
authors.lastname: Zhang
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D053759:Interleukin-23 / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D007719:Knee Joint / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis; D010024:Osteoporosis / Q000503:physiopathology; D053245:RANK Ligand / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D013583:Synovial Membrane / Q000503:physiopathology; D058504:Th17 Cells / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D052242:Adiponectin; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053245:RANK Ligand; D012333:RNA, Messenger; D000097043:Interleukin-22; C505689:Tnfsf11 protein, mouse