title: Periostin increases migration and proliferation of human periodontal ligament fibroblasts challenged by tumor necrosis factor -α and Porphyromonas gingivalis lipopolysaccharides.
abstract: BACKGROUND
  In the chronic established periodontal lesion, the proliferation and migration potential of periodontal ligament (PDL) cells are significantly compromised. Thus, the progressive loss of tissue integrity is favored and normal healing and regeneration compromised. Periostin, a known PDL marker, modulates cell-matrix interactions, cell behavior, as well as the matrix biomechanics and PDL homeostasis.
  
  
  OBJECTIVE
  To evaluate whether periostin restores the regenerative potential of PDL cells in terms of proliferation, migration, and activation of survival signaling pathways after being challenged by Porphyromonas gingivalis lipopolysaccharides and tumor necrosis factor alpha α.
  
  
  METHODS
  Human PDL (hPDL) cells were cultured under different conditions: control, periostin (50 or 100 ng/mL), and fibroblast growth factor 2 (10 ng/mL) to evaluate cell proliferation (by Ki67), cell migration (by scratch assays) and PI3K/AKT/mTOR pathway activation (by western blot analyses of total AKT, phospho-AKT and PS6). A different set of cultures was challenged by adding tumor necrosis factor alpha α (10 ng/mL) and P. gingivalis lipopolysaccharides (200 ng/mL) to evaluate the effects of periostin as described above.
  
  
  RESULTS
  Periostin significantly increased cell proliferation (twofold), migration (especially at earlier time points and low dose) and activation of survival signaling pathway (higher phosphorylation of AKT and PS6). Furthermore, periostin promoted similar cellular effects even after being challenged with proinflammatory cytokines and bacterial virulence factors.
  
  
  CONCLUSIONS
  Periostin acts as an important modulator of hPDL cell-matrix dynamics. It modulates hPDL proliferation, migration and PI3K/AKT/mTOR pathway. It also helps in overcoming the altered biological phenotype that chronic exposure to periodontal pathogens and proinflammatory cytokines produce in hPDL cells.
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA; Department of Oral Surgery and Implant Dentistry, School of Dentistry, University of Granada, Granada, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Padial-Molina
authors.forename: S L
authors.initials: SL
authors.lastname: Volk
authors.forename: H F
authors.initials: HF
authors.lastname: Rios
mesh_terms: D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects; D010766:Phosphorylation; D016966:Porphyromonas gingivalis / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015815:Cell Adhesion Molecules; D016222:Fibroblast Growth Factor 2; D019394:Ki-67 Antigen; D008070:Lipopolysaccharides; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; C512835:POSTN protein, human; C546842:MTOR protein, human
keywords: cell migration; cell proliferation; periodontal disease; periodontal ligament; periostin