title: Periostin inhibits hypoxia-induced apoptosis in human periodontal ligament cells via TGF-β signaling.
abstract: Periostin (POSTN) is an extracellular matrix protein expressed predominantly in periodontal ligament (PDL) cells. The aim of this study was to investigate the effects of POSTN on human PDL cell apoptosis under hypoxic conditions. The percentage of apoptotic PDL cells under hypoxia was increased significantly when the endogenous POSTN gene was silenced using siRNA, but decreased when cells were treated with recombinant human POSTN (rhPOSTN), or when mouse Postn was overexpressed in vitro. Silencing POSTN during hypoxia decreased the expression of HIF prolyl-hydroxylase 2 (PHD2), but increased HIF-1α protein level. Conversely, treating hypoxic cells with rhPOSTN or overexpressing Postn increased PHD2 expression but decreased HIF-1α levels. The addition of rhPOSTN in the absence of a TGF-β receptor inhibitor (SB525334) significantly decreased hypoxia-induced apoptosis, while the effects of rhPOSTN were abolished when cells were co-treated with SB525334. Consistent with this, the phosphorylation of SMAD2 was increased in hypoxic PDL cells by the knockdown of POSTN, but decreased by treatment with rhPOSTN. Under normoxia, the PHD2 expression, HIF-1α level, and apoptosis were unaffected by POSTN siRNA, rhPOSTN, or Postn overexpression. These findings suggest that, under hypoxic conditions, POSTN regulates PHD2 expression and HIF-1α levels by modulating TGF-β1 signaling, leading to decreased apoptosis.
authors.affiliation: Section of Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Paveenarat
authors.initials: P
authors.lastname: Aukkarasongsup
authors.forename: Naoto
authors.initials: N
authors.lastname: Haruyama
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Momotoshi
authors.initials: M
authors.lastname: Shiga
authors.forename: Keiji
authors.initials: K
authors.lastname: Moriyama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010513:Periodontal Ligament / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051785:Smad Proteins / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C090121:BNIP3 protein, human; D015815:Cell Adhesion Molecules; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; C512835:POSTN protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C490190:EGLN1 protein, human; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases
keywords: Apoptosis; HIF-1α; Hypoxia; Periodontal ligament; Periostin; TGF-β1