title: Induction of S100A4 in periodontal ligament cells enhances osteoclast formation.
abstract: BACKGROUND
  An increase in the expression of S100A4 has been reported in various inflammatory diseases. However, little is known about the association between periodontal inflammation and S100A4 expression. The aims of this study were to investigate changes in S100A4 expression in human periodontal ligament (hPDL) cells in response to inflammatory stimuli and to describe a possible mechanism underlying the change.
  
  
  METHODS
  Human PDL cells were treated with lipopolysaccharide (LPS) and the level of S100A4 was analyzed by real-time RT-PCR and Western blotting. LPS was added to co-cultures of hPDL and osteoclast progenitor cells under osteoclastogenic condition and the formation of osteoclasts was assessed. Alternatively, progenitor cells were directly treated with recombinant S100A4 for evaluation of osteoclastogenesis. The activity of nuclear factor kappaB (NFκB) was examined by Western blotting for phosphorylated forms of inhibitor kappaB (IκB) and p65. An NFκB inhibitor was added to the culture of hPDL cells with LPS and the level of S100A4 was measured by real-time RT-PCR.
  
  
  RESULTS
  We found that LPS stimulation resulted in a significant increase of S100A4 expression in hPDL cells. S100A4 protein secretion from hPDL cells was also increased. The enhanced expression of S100A4 in hPDL cells under inflammatory conditions led to stimulation of the generation of osteoclasts. In addition, direct S100A4 treatment stimulated osteoclastogenesis. The underlying mechanism for the increased S100A4 expression in hPDL cells was activation of the NFκB signaling pathway.
  
  
  CONCLUSIONS
  Our results suggest that bone destruction in periodontitis might be associated with increased S100A4 expression in hPDL cells.
authors.affiliation: Department of Orthodontics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Su-Jung
authors.initials: SJ
authors.lastname: Mah
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Haemin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Orthodontics, Dental College, Kyung Hee University, Seoul, Korea.
authors.forename: Yoon-Goo
authors.initials: YG
authors.lastname: Kang
authors.affiliation: Department of Orthodontics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Seung-Hak
authors.initials: SH
authors.lastname: Baek
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Department of Orthodontics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea. Electronic address: whlim@snu.ac.kr.
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Lim
mesh_terms: D015153:Blotting, Western; D018920:Coculture Techniques; D006801:Humans; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism*; D010513:Periodontal Ligament / Q000166:cytology*; D060888:Real-Time Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human
keywords: Inflammation; NFκB; Osteoclastogenesis; Periodontal ligament cells; S100A4