title: Interleukin-6 inhibits early differentiation of ATDC5 chondrogenic progenitor cells.
abstract: Interleukin (IL)-6 is a causative agent of systemic juvenile idiopathic arthritis (sJIA), a chronic inflammatory disease complicated with severe growth impairment. Recent trials of anti-IL-6 receptor monoclonal antibody, tocilizumab, indicated that tocilizumab blocks IL-6/IL-6 receptor-mediated inflammation, and induces catch-up growth in children with sJIA. This study evaluates the effects of IL-6 on chondrogenesis by ATDC5 cells, a clonal murine chondrogenic cell line that provides an excellent model for studying endochondral ossification at growth plate. ATDC5 cells were examined for the expression of IL-6 receptor and gp130 by fluorescence-activated cell sorting analysis. Recombinant murine IL-6 was added to ATDC5 cultures to observe cell differentiation, using a quantitative RT-PCR for the chondrogenic differentiation markers type II collagen, aggrecan, and type X collagen. To block IL-6, the anti-mouse IL-6 receptor monoclonal antibody MR16-1 was added. As a result, the cells expressed IL-6 receptor and gp130. The expression of chondrogenic differentiation marker gene was reduced by IL-6, but this was abrogated by MR16-1. We conclude that IL-6 inhibits early chondrogenesis of ATDC5 cells suggesting that IL-6 may affect committed stem cells at a cellular level during chondrogenic differentiation of growth plate chondrocytes, and that IL-6 may be a cellular-level factor in growth impairment in sJIA.
authors.affiliation: Department of Pediatrics, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. shoko92@bf6.so-net.ne.jp
authors.forename: Shoko
authors.initials: S
authors.lastname: Nakajima
authors.forename: Takuya
authors.initials: T
authors.lastname: Naruto
authors.forename: Takako
authors.initials: T
authors.lastname: Miyamae
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Imagawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Mori
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nishimaki
authors.forename: Shumpei
authors.initials: S
authors.lastname: Yokota
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002356:Cartilage / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C494200:Il6st protein, mouse; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130