title: Lactoferrin inhibits infection-related osteoclastogenesis without interrupting compressive force-related osteoclastogenesis.
abstract: BACKGROUND
  Control of periodontal tissue inflammation during orthodontic treatment is very important in achieving a favourable therapeutic goal. We previously demonstrated that orally applied bovine lactoferrin (bLF) inhibited LPS-induced bone resorption but not orthodontic force-induced tooth movement in vivo. This study is designed to examine the underlying mechanism of it.
  
  
  METHODS
  We examined the inhibitory effects of bLF on the expression of RANKL, OPG, TNF-α and COX-2 in osteoblasts loaded with compressive stress (CS) in comparison with LPS stimulated osteoblasts. Formation of osteoclasts was evaluated by co-culture system.
  
  
  RESULTS
  Both CS- and LPS-applications upregulated COX-2 and RANKL but downregulated OPG. TNF-α was upregulated in LPS-stimulated osteoblasts but downregulated in CS-loaded osteoblasts. NS398 (a specific inhibitor of COX-2) significantly inhibited CS-induced RANKL-upregulation but not LPS-induced RANKL upregulation, indicating a critical role of COX-2/PGE2 pathway in CS-induced osteoclastogenesis. bLF significantly downregulated LPS-induced upregulation of RANKL and eliminated OPG suppression but not affected in CS-induced changes. Moreover, bLF significantly decreased LPS-induced osteoclast formation, whereas bLF had no effect on PGE2-induced osteoclast formation.
  
  
  CONCLUSIONS
  bLF can effectively suppress harmful bone destruction associated with periodontitis without inhibiting bone remodelling by CS-loading. Therefore, oral administration of bLF may be highly beneficial for control of periodontitis in orthodontic patients.
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan. Electronic address: inubushi-t@hiroshima-u.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Inubushi
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan; Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kawazoe
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Miyauchi
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yanagisawa
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Subarnbhesaj
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Chanbora
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: N F
authors.initials: NF
authors.lastname: Ayuningtyas
authors.affiliation: R&D Division, Sunstar Inc, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ishikado
authors.affiliation: Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Sciences, Tokushima, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Tanaka
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan. Electronic address: ttakata@hiroshima-u.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Takata
mesh_terms: D001862:Bone Resorption; D002460:Cell Line; D019245:Compressive Strength; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects*; D010010:Osteoclasts / Q000187:drug effects*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D007781:Lactoferrin
keywords: Anti-inflammatory agents; Bone biology; Cytokine(s); Lactoferrin; Osteoblast(s); Periodontitis