title: Interleukin-1β induces fibroblast growth factor 2 expression and subsequently promotes endothelial progenitor cell angiogenesis in chondrocytes.
abstract: Arthritis is a process of chronic inflammation that results in joint damage. IL (interleukin)-1β is an inflammatory cytokine that acts as a key mediator of cartilage degradation, and is abundantly expressed in arthritis. Neovascularization is one of the pathological characteristics of arthritis. However, the role of IL-1β in the angiogenesis of chondrocytes remains unknown. In the present study, we demonstrate that stimulating chondrocytes (ATDC5) with IL-1β increased the expression of FGF (fibroblast growth factor)-2, a potent angiogenic inducer, and then promoted EPC (endothelial progenitor cell) tube formation and migration. In addition, FGF-2-neutralizing antibody abolished ATDC5-conditional medium-mediated angiogenesis in vitro, as well as its angiogenic effects in the CAM (chick chorioallantoic membrane) assay and Matrigel plug nude mice model in vivo. IHC (immunohistochemistry) staining from a CIA (collagen-induced arthritis) mouse model also demonstrates that arthritis increased the expression of IL-1β and FGF-2, as well as EPC homing in articular cartilage. Moreover, IL-1β-induced FGF-2 expression via IL-1RI (type-1 IL-1 receptor), ROS (reactive oxygen species) generation, AMPK (AMP-activated protein kinase), p38 and NF-κB (nuclear factor κB) pathway has been demonstrated. On the basis of these findings, we conclude that IL-1β promotes FGF-2 expression in chondrocytes through the ROS/AMPK/p38/NF-κB signalling pathway and subsequently increases EPC angiogenesis. Therefore IL-1β serves as a link between inflammation and angiogenesis during arthritis.
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Szu-Yu
authors.initials: SY
authors.lastname: Chien
authors.affiliation: Department of Orthopaedic Surgery, China Medical University Beigang Hospital, Yun-Lin County, Taiwan School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chun-Yin
authors.initials: CY
authors.lastname: Huang
authors.affiliation: School of Medicine, China Medical University, Taichung, Taiwan Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan Department of Orthopedic Surgery, Taichung Veterans General Hospital, Taichung, Taiwan chtang@mail.cmu.edu.tw) ymlin@vghtc.gov.tw.
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Lin
authors.affiliation: School of Medicine, China Medical University, Taichung, Taiwan Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan chtang@mail.cmu.edu.tw) ymlin@vghtc.gov.tw.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002645:Chickens; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018123:Receptors, Interleukin; D016222:Fibroblast Growth Factor 2; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases
keywords: FGF-2; IL-1β; arthritis; cartilage; chondrocyte; neovascularization
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