title: Inhibitory effects of orally administrated liposomal bovine lactoferrin on the LPS-induced osteoclastogenesis.
abstract: Bovine lactoferrin (bLF) modulates the production of proinflammatory cytokines including tumor necrosis factor (TNF)-alpha, and may thus control alveolar bone destruction associated with periodontitis. In this study, the effects of bLF on mRNA expression in lipopolysaccharide (LPS)-stimulated osteoblasts (OBs) and on LPS-induced osteoclastogenesis were examined. The inhibitory effects of oral administration of liposomal-bLF (L-bLF), which improved the robustness of bLF to digestive enzymes, on alveolar bone resorption using LPS-induced periodontitis rat model are also reported. Three groups of 7-week-old male Wistar rats were treated with L-bLF (L-bLF group), bLF (bLF group), or the vehicle (control group) in drinking water (n=6 in each group). On day 7, LPS was topically applied into the gingival sulcus. Number of osteoclasts and immunoexpression of TNF-alpha were analyzed. The bLF inhibited the upregulation of TNF-alpha-mRNA- and upregulation of receptor activator of NF kappaB (RANKL)-mRNA expression and eliminated downregulation of osteoprotegerin (OPG)-mRNA expression in LPS-stimulated OBs and reduced LPS-induced osteoclastogenesis in co-culture with primary OBs and bone marrow cells. In the control group, the number of osteoclasts increased after LPS treatment. The number of osteoclasts that appeared along the alveolar bone margin was significantly reduced (P<0.01) in the L-bLF but not in the bLF group. Furthermore, L-bLF suppressed upregulation of TNF-alpha immunoexpression in periodontal tissue and TNF-alpha and interleukin (IL)-1 beta-mRNA level in gingival tissue. The results of this study indicate that oral administration of L-bLF significantly reduces alveolar bone resorption induced by LPS stimulation through inhibition of TNF-alpha production and modulation of RANKL/OPG balance in OBs. It is suggested that L-bLF could be a potent therapeutic and preventive agent for attenuating alveolar bone destruction in periodontitis patients.
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan.
authors.forename: Eizo
authors.initials: E
authors.lastname: Yamano
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Miyauchi
authors.forename: Hisako
authors.initials: H
authors.lastname: Furusyo
authors.forename: Aki
authors.initials: A
authors.lastname: Kawazoe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishikado
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Makino
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tanne
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
mesh_terms: D016301:Alveolar Bone Loss / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D001862:Bone Resorption / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D002417:Cattle; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D005881:Gingiva / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007781:Lactoferrin / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010006:Osteoblasts / Q000276:immunology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D053244:Osteoprotegerin / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D010518:Periodontitis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D053244:Osteoprotegerin; D053246:Receptor Activator of Nuclear Factor-kappa B; D014409:Tumor Necrosis Factor-alpha; D007781:Lactoferrin