title: Interleukin-1β Suppresses the Transporter Genes Ank and Ent1 Expression in Stromal Progenitor Cells Retaining Mineralization.
abstract: Heterotopic ossification (HO) in various tissues evokes clinical problems. Inflammatory responses of the stromal progenitor cells may be involved in its etiology. Previous report indicated that pro-inflammatory cytokines including IL-1β enhanced the in vitro calcification of human mesenchymal stem cells (MSCs), by suppressing the expression of ectonucleotide pyrophosphatase/phosphodiesterase-1 gene (ENPP1). However, possible contribution of other related factors had not been investigated. Here, we investigated the expression of regulators of extracellular pyrophosphate and nucleosides including Enpp1, Nt5e, Ank, Enptds, and Ent1, examining various connective tissue stromal progenitor cells, including bone marrow stromal cells and synovium derived cells from mouse, or bone marrow MSCs from human. Consistent with previous studies, we observed characteristic suppression of the osteoblastic marker genes by IL-1β during the osteogenic culture for 20 days. In addition, we observed a reduced expression of the important transporter genes, Ank and Ent1, whereas the alteration in Enpp1 and Nt5e levels was not always consistent among the cell types. Our results suggest that IL-1β suppresses not only the osteoblastic but also the negative regulators of soft-tissue calcification, including Ank and Ent1 in stromal progenitor cells, which may contribute to the mechanisms of HO in various disorders.
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 5-45 1-Chome, Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan. ezura.mph@mri.tmd.ac.jp.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 5-45 1-Chome, Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 5-45 1-Chome, Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan.
authors.forename: Arina
authors.initials: A
authors.lastname: Hatta
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 5-45 1-Chome, Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Izu
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 5-45 1-Chome, Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects / Q000502:physiology; D002114:Calcinosis / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D028061:Phosphate Transport Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects*
chemical_list: D033721:Equilibrative Nucleoside Transporter 1; D053583:Interleukin-1beta; D028061:Phosphate Transport Proteins; C498476:SLC29A1 protein, mouse; C410982:ank protein, mouse
keywords: Bio-mineralization; Gene expression; Mesenchymal stem cell; Osteogenesis