title: Muramyl dipeptide enhances lipopolysaccharide-induced osteoclast formation and bone resorption through increased RANKL expression in stromal cells.
abstract: Lipopolysaccharide (LPS) is bacterial cell wall component capable of inducing osteoclast formation and pathological bone resorption. Muramyl dipeptide (MDP), the minimal essential structural unit responsible for the immunological activity of peptidoglycans, is ubiquitously expressed by bacterium. In this study, we investigated the effect of MDP in LPS-induced osteoclast formation and bone resorption. LPS was administered with or without MDP into the supracalvariae of mice. The number of osteoclasts, the level of mRNA for cathepsin K and tartrate-resistant acid phosphatase (TRAP), the ratio of the bone destruction area, the level of tartrate-resistant acid phosphatase form 5b (TRACP 5b), and C-terminal telopeptides fragments of type I collagen as a marker of bone resorption in mice administrated both LPS and MDP were higher than those in mice administrated LPS or MDP alone. On the other hand, MDP had no effect on osteoclastogenesis in parathyroid hormone administrated mice. MDP enhanced LPS-induced receptor activator of NF-κB ligand (RANKL) expression and Toll-like receptor 4 (TLR4) expression in vivo and in stromal cells in vitro. MDP also enhanced LPS-induced mitogen-activated protein kinase (MAPK) signaling, including ERK, p38, and JNK, in stromal cells. These results suggest that MDP might play an important role in pathological bone resorption in bacterial infection diseases.
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: Hideki
authors.identifier: 0000-0003-3249-4247
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: 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: Tomo
authors.initials: T
authors.lastname: Aonuma
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Takada
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: Teruko
authors.initials: T
authors.lastname: Takano-Yamamoto
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000135:Acid Phosphatase / Q000235:genetics; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D056657:Cathepsin K / Q000235:genetics; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D053245:RANK Ligand / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism*; D000071681:Tartrate-Resistant Acid Phosphatase; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D024042:Collagen Type I; D007527:Isoenzymes; D008070:Lipopolysaccharides; D010281:Parathyroid Hormone; D053245:RANK Ligand; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; C505689:Tnfsf11 protein, mouse; D051197:Toll-Like Receptor 4; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K