title: Changes in the spatial distribution of sclerostin in the osteocytic lacuno-canalicular system in alveolar bone due to orthodontic forces, as detected on multimodal confocal fluorescence imaging analyses.
abstract: OBJECTIVE
  Mechanical loading on the bone is sensed by osteocytes. Sclerostin is a molecule secreted by osteocytes that is downregulated by mechanical loading; therefore, its expression level is a potent sensor that indicates the spatial transduction of biomechanical properties in bone. This study applied macroconfocal microscopy to observe the spatial response of alveolar bone to orthodontic forces after immunofluorescence using anti-sclerostin antibodies.
  
  
  METHODS
  Orthodontic tooth movement with the Ni-Ti closed-coil spring was applied between the upper bilateral incisors and the left first molar of mice. Four days after this application, the animals were subjected to multimodal confocal fluorescence imaging analyses.
  
  
  RESULTS
  Obvious downregulation of sclerotin in the osteocytic lacuna-canalicular system (LCS) was observed specifically in tensile sites of alveolar bone. Confocal-based three-dimensional fluorescence morphometry further quantitatively demonstrated that the distribution and expression of sclerostin in the tensile sites was significantly reduced compared to that observed in the corresponding control sites. Interestingly, the levels of sclerotin signals in the compression sites were significantly higher than those observed in the control sites, although the distribution of sclerotin was not significantly different.
  
  
  CONCLUSIONS
  Our observations suggest that spatial changes in the level and distribution of sclerostin in the alveolar LCS trigger successive bone remodelling due to orthodontic tooth movement. The multimodal confocal imaging analyses applied in this work will enhance comprehensive understanding regarding the spatial regulation of molecules of interest from the tissue to the cellular level.
authors.affiliation: Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8549, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Nishiyama
authors.affiliation: Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8549, Japan; Section of Maxillofacial Orthognathics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8549, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8549, Japan; Division of Bio-Imaging, Proteo-Science Center (PROS), Ehime University, Ehime, 791-0295, Japan.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine for Pathogenesis, Graduate School of Medicine, Ehime University, Ehime, 791-0295, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Saitou
authors.affiliation: Division of Bio-Imaging, Proteo-Science Center (PROS), Ehime University, Ehime, 791-0295, Japan; Department of Molecular Medicine for Pathogenesis, Graduate School of Medicine, Ehime University, Ehime, 791-0295, Japan; Translational Research Center and Artificial Joint Integrated Center, Ehime University Hospital, Ehime, 791-0295, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Section of Maxillofacial Orthognathics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8549, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Moriyama
authors.affiliation: Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8549, Japan. Electronic address: akira.mpa@tmd.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaguchi
authors.affiliation: Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8549, Japan; Division of Bio-Imaging, Proteo-Science Center (PROS), Ehime University, Ehime, 791-0295, Japan; Translational Research Center and Artificial Joint Integrated Center, Ehime University Hospital, Ehime, 791-0295, Japan. Electronic address: iimura@m.ehime-u.ac.jp.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Iimura
mesh_terms: D000539:Alveolar Process / Q000166:cytology*; D000818:Animals; D001696:Biomechanical Phenomena; D015536:Down-Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010011:Osteocytes / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D013718:Tensile Strength; D014087:Tooth Movement Techniques / Q000379:methods*
chemical_list: D011506:Proteins; C013247:sclerotin
keywords: Bone remodelling; Imaging; Mechanotransduction; Osteoblast; Osteoclast; Osteocyte