title: Inhibition of osteoclastogenesis by osteoblast-like cells genetically engineered to produce interleukin-10.
abstract: Bone destruction at inflamed joints is an important complication associated with rheumatoid arthritis (RA). Interleukin-10 (IL-10) may suppress not only inflammation but also induction of osteoclasts that play key roles in the bone destruction. If IL-10-producing osteoblast-like cells are induced from patient somatic cells and transplanted back into the destructive bone lesion, such therapy may promote bone remodeling by the cooperative effects of IL-10 and osteoblasts. We transduced mouse fibroblasts with genes for IL-10 and Runx2 that is a crucial transcription factor for osteoblast differentiation. The IL-10-producing induced osteoblast-like cells (IL-10-iOBs) strongly expressed osteoblast-specific genes and massively produced bone matrix that were mineralized by calcium phosphate in vitro and in vivo. Culture supernatant of IL-10-iOBs significantly suppressed induction of osteoclast from RANKL-stimulated Raw264.7 cells as well as LPS-induced production of inflammatory cytokine by macrophages. The IL-10-iOBs may be applicable to novel cell-based therapy against bone destruction associated with RA.
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Fujioka
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tsunao
authors.initials: T
authors.lastname: Kishida
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Akika
authors.initials: A
authors.lastname: Ejima
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Fujii
authors.affiliation: Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Murakami
authors.affiliation: Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Rheumatic Diseases and Joint Function, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Seno
authors.affiliation: Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Aihiro
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kohno
authors.affiliation: Department of Orthopaedics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Oda
authors.affiliation: Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Orthopaedics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawahito
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: mazda@koto.kpu-m.ac.jp.
authors.forename: Osam
authors.initials: O
authors.lastname: Mazda
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000150:complications; D001857:Bone Matrix / Q000276:immunology; D016723:Bone Remodeling; D001862:Bone Resorption / Q000209:etiology / Q000628:therapy*; D002113:Calcification, Physiologic; D002130:Calcium Phosphates / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D005818:Genetic Engineering; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D010006:Osteoblasts / Q000276:immunology*; D010010:Osteoclasts / Q000276:immunology*; D010012:Osteogenesis / Q000235:genetics; D053245:RANK Ligand / Q000276:immunology; D014161:Transduction, Genetic
chemical_list: D002130:Calcium Phosphates; D050659:Core Binding Factor Alpha 1 Subunit; D008070:Lipopolysaccharides; D053245:RANK Ligand; C493716:Runx2 protein, mouse; D016753:Interleukin-10; C020243:calcium phosphate
keywords: Gene therapy; Inflammation; Interleukin-10; Osteoblast; Rheumatoid arthritis