title: The roles of TNFR1 in lipopolysaccharide-induced bone loss: dual effects of TNFR1 on bone metabolism via osteoclastogenesis and osteoblast survival.
abstract: LPS (lipopolysaccharide), a major constituent of Gram-negative bacteria, regulates proliferation and differentiation of osteoclasts directly or indirectly. This study sought to investigate the functions of the RANK/RANKL pathway in LPS-induced bone loss in vivo. Wild-type mice or TNFR1-/- mice were injected LPS with or without osteoprotegerin (OPG) and analyzed histologically. Bone volume was reduced by LPS injection in all groups, and OPG administration prevented the LPS-induced bone loss regardless of genotypes. LPS-induced enhancement of osteoclastogenesis in wild-type mice was blocked by OPG administration. LPS or OPG did not affect osteoclastogenesis in TNFR1-/- mice. Interestingly, osteoblast surface was remarkably reduced in LPS-treated TNFR1-/- mice as a result of enhanced osteoblast apoptosis. TRAIL, induced by TNF-alpha in BMC, triggered apoptosis of primary osteoblast only when TNFR1 signal was ablated in vitro. In conclusion, RANK signaling plays a prominent role in osteoclastogenesis downstream of LPS. Furthermore, TNFR1 regulates bone metabolism through not only the regulation of osteoclast differentiation but also osteoblast survival.
authors.affiliation: Division of Veterinary Surgery, Department of Veterinary Science, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ochi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tagawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shinomiya
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Asou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D001862:Bone Resorption / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004347:Drug Interactions; D005434:Flow Cytometry; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D053244:Osteoprotegerin / Q000378:metabolism / Q000494:pharmacology; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics* / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; D053221:TNF-Related Apoptosis-Inducing Ligand; C506030:TNFRSF11B protein, human; C505687:Tnfrsf11a protein, mouse; C506236:Tnfrsf1a protein, mouse; C505654:Tnfsf10 protein, mouse; C505689:Tnfsf11 protein, mouse