title: IL-37 inhibits lipopolysaccharide-induced osteoclast formation and bone resorption in vivo.
abstract: IL-37 is a newly defined member of the IL-1 cytokine family. It has been reported that IL-37 inhibited innate immunity and inflammatory responses in autoimmune diseases and tumors. IL-37 also inhibited Lipopolysaccharide (LPS)-induced immunological reaction. LPS is a bacterial cell wall component that is capable of inducing osteoclast formation and pathological bone resorption. However, there is no study to investigate the effect of IL-37 on LPS-induced osteoclast formation and bone resorption. The purpose of this study is to investigate the effect of IL-37 in LPS-induced osteoclast formation and bone resorption. LPS was administrated with or without IL-37 by subcutaneous injection on mice calvariae. The number of osteoclasts, the level of tartrate-resistant acid phosphatase (TRAP) and cathepsin K mRNA, the ratio of the bone resorption pits and the level of C-terminal telopeptide fragments of type I collagen cross-Links as a marker of bone resorption in mice administrated both LPS and IL-37 were lower than that in mice administrated LPS alone. Real-time RT-PCR was performed to analyze osteoclast related cytokines RANKL, TNF-α and IL-1β mRNA levels in vivo. RANKL, TNF-α and IL-1β mRNAs were increased in the LPS alone administrated mice as compared with PBS administrated groups. On the other hand, RANKL, TNF-α and IL-1β mRNAs were inhibited in the IL-37 and LPS administrated mice as compared with LPS alone administrated group. In vitro analysis, there was no effect of IL-37 in RANKL-induced osteoclast formation, TNF-α-induced osteoclast formation and cell viability from bone marrow macrophages as osteoclast precursor and LPS-induced RANKL expression from stromal cells. These results indicated that IL-37 inhibited LPS-induced osteoclast formation and bone resorption via inhibition of LPS-induced osteoclast related cytokines, but might not directly inhibit osteoclast formation on osteoclast precursor and RANKL expression on stromal cells.
authors.affiliation: Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Jafari
authors.initials: J
authors.lastname: Saeed
authors.affiliation: Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kitaura
authors.affiliation: Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ishida
authors.affiliation: Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Sugisawa
authors.affiliation: Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ochi
authors.affiliation: Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kishikawa
authors.affiliation: Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Electronic address: t-yamamo@m.tohoku.ac.jp.
authors.forename: Teruko
authors.initials: T
authors.lastname: Takano-Yamamoto
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000276:immunology*; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000276:immunology*; D010455:Peptides / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D016207:Cytokines; C508587:IL37 protein, human; D018836:Inflammation Mediators; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K
keywords: Cytokine; IL-37; LPS; Osteoclast