title: Cytokines induce MMP-3-regulated proliferation of embryonic stem cell-derived odontoblast-like cells.
abstract: OBJECTIVE
  Matrix metalloproteinase (MMP)-3 expression increases after pulpectomy and accelerates angiogenesis in rat dental pulp by an uncharacterised mechanism. Odontoblasts, a major component of dental pulp, could represent a therapeutic target. We investigated whether MMP-3 activity is induced by cytokines and/or is associated with cell proliferation and apoptosis in embryonic stem cell-derived odontoblast-like cells.
  
  
  METHODS
  We used reverse transcriptase polymerase chain reaction, western blotting, an MMP-3 activity assay, a BrdU-cell proliferation enzyme-linked immunosorbent assay and DNA fragmentation analysis to evaluate siRNA-mediated downregulation of MMP-3 expression and activity, and any changes in the proliferative and apoptotic responses associated with this reduced expression.
  
  
  RESULTS
  Pro-inflammatory cytokines (interleukin-1β, tumour necrosis factor-α and interferon-γ, at relatively low concentrations) induced MMP-3 mRNA and protein expression, and increased MMP-3 activity and cell proliferation, but not apoptosis. MMP-3 silencing produced a potent and significant suppression of cytokine-induced MMP-3 expression and activity, decreased cell proliferation and increased apoptosis. These effects were rescued by application of exogenous MMP-3.
  
  
  CONCLUSIONS
  Our results suggest that pro-inflammatory cytokines induce MMP-3-regulated cell proliferation and anti-apoptosis effects in odontoblast-like cells derived from embryonic stem cells, in addition to their well-documented destructive role in inflammation.
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Ozeki
authors.forename: H
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: R
authors.initials: R
authors.lastname: Kawai
authors.forename: T
authors.initials: T
authors.lastname: Hiyama
authors.forename: K
authors.initials: K
authors.lastname: Nakata
authors.forename: M
authors.initials: M
authors.lastname: Mogi
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology*; D019278:Matrix Metalloproteinase 3 / Q000502:physiology*; D051379:Mice; D009804:Odontoblasts / Q000166:cytology* / Q000187:drug effects; D011506:Proteins
chemical_list: D016207:Cytokines; D011506:Proteins; C118748:reducing agent and tunicamycin-responsive protein, human; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse
keywords: cytokines; embryonic stem cells; inflammation; matrix metalloproteinase; odontoblast