title: Stimulation of periodontal ligament stem cells by dentin matrix protein 1 activates mitogen-activated protein kinase and osteoblast differentiation.
abstract: BACKGROUND
  Periodontitis can ultimately result in tooth loss. Many natural and synthetic materials have been tried to achieve periodontal regeneration, but the results remain variable and unpredictable. We hypothesized that exogenous treatment with dentin matrix protein 1 (DMP1) activates specific genes and results in phenotypic and functional changes in human periodontal ligament stem cells (hPDLSCs).
  
  
  METHODS
  hPDLSCs were isolated from extracted teeth and cultured in the presence or absence of DMP1. Quantitative polymerase chain reactions were performed to analyze the expression of several genes involved in periodontal regeneration. hPDLSCs were also processed for immunocytochemical and Western blot analysis using phosphorylated extracellular signal-regulated kinase (pERK) and ERK antibodies. Alkaline phosphatase and von Kossa staining were performed to characterize the differentiation of hPDLSCs into osteoblasts. Field emission scanning electron microscopic analysis of the treated and control cell cultures were also performed.
  
  
  RESULTS
  Treatment with DMP1 resulted in the upregulation of genes, such as matrix metalloproteinase-2, alkaline phosphatase, and transforming growth factor β1. Activation of ERK mitogen-activated protein kinase signaling pathway and translocation of pERK from the cytoplasm to the nucleus was observed. Overall, DMP1-treated cells showed increased expression of alkaline phosphatase, increased matrix, and mineralized nodule formation when compared with untreated controls.
  
  
  CONCLUSIONS
  DMP1 can orchestrate a coordinated expression of genes and phenotypic changes in hPDLSCs by activation of the ERK signaling pathway, which may provide a valuable strategy for tissue engineering approaches in periodontal regeneration.
authors.affiliation: Department of Periodontology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Chandrasekaran
authors.forename: Amsaveni
authors.initials: A
authors.lastname: Ramachandran
authors.forename: Asha
authors.initials: A
authors.lastname: Eapen
authors.forename: Anne
authors.initials: A
authors.lastname: George
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000494:pharmacology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010750:Phosphoproteins / Q000494:pharmacology / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport; D011994:Recombinant Proteins; D012038:Regeneration / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects
chemical_list: C513309:DMP1 protein, human; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D020928:Mitogen-Activated Protein Kinases