title: S100A4 inhibition by RNAi up-regulates osteoblast related genes in periodontal ligament cells.
abstract: Periodontal ligament (PDL) is a thin fibrous connective tissue located between alveolar bone and cementum that remains unmineralized physiologically. It is thus thought that PDL cells possess mechanisms to inhibit mineralization. It has been demonstrated that S100A4, a member of the S100 calcium-binding protein family, is synthesized and secreted by PDL cells, and that it may act as an inhibitor of mineralization. However, the mechanisms of action of S100A4 in mineralization have not been thoroughly clarified. In the present study we investigated the effects of S100A4 inhibition by a short interfering RNA (siRNA) on the expression of osteoblast related genes by human PDL cells. Inhibition of S100A4 by siRNA resulted in increased expression of osteoblastic markers such as osteopontin and osteocalcin, and the osteoblast-specific transcription factors, Runx2/Cbfa1 and Osterix. These results indicate that S100A4 suppresses the expression of osteoblastic genes in PDL cells and may thus inhibit mineralization in the PDL.
authors.affiliation: Periodontology, Department of Hard Tissue Engineering, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. chiyu.peri@tmd.ac.jp
authors.forename: Chiyu
authors.initials: C
authors.lastname: Kato
authors.forename: Takehisa
authors.initials: T
authors.lastname: Kojima
authors.forename: Motohiro
authors.initials: M
authors.lastname: Komaki
authors.forename: Kaori
authors.initials: K
authors.lastname: Mimori
authors.forename: Wagner R
authors.initials: WR
authors.lastname: Duarte
authors.forename: Keizo
authors.initials: K
authors.lastname: Takenaga
authors.forename: Isao
authors.initials: I
authors.lastname: Ishikawa
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015675:Osteocalcin / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D053495:Osteopontin; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D004268:DNA-Binding Proteins; C493709:RUNX2 protein, human; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D015675:Osteocalcin; D053495:Osteopontin; C077591:S100A4 protein, human