title: Effect of carnosine on runt-related transcription factor-2/core binding factor alpha-1 and Sox9 expressions of human periodontal ligament cells.
abstract: BACKGROUND
  Previous studies have reported that beta-alanyl-l-histidine (carnosine) enhanced the process of wound healing by stimulating effusion at the initial stage of inflammation, and also enhanced runt-related transcription factor-2/core binding factor alpha-1 (RUNX2/Cbfa1), Sox9, bone morphogenetic protein-2 (BMP-2) and BMP-7 expressions of human periodontal ligament cells.
  
  
  OBJECTIVE
  In order to clarify the relationship between RUNX2/Cbfa1 or Sox9 expressions and BMP-2 or BMP-7 expressions enhanced by carnosine, we determined the effect of carnosine on the expression of BMP receptors and activation of their downstream signaling molecules in human periodontal ligament cells.
  
  
  METHODS
  Human periodontal ligament cells were cultured with alpha-minimum essential medium containing 10% fetal bovine serum with or without 10(-4) or 10(-5) m carnosine for up to 10 days. The gene expression of BMP receptors, RUNX2/Cbfa1 and Sox9 was measured using semiquantitative reverse transcription-polymerase chain reaction. Phosphorylation of Smad1 was determined using a western blot analysis.
  
  
  RESULTS
  Alkaline phosphatase activity increased in cultures with carnosine. Among the BMP receptors, expression of ActR-I and BMPR-II increased in cultures with carnosine, whereas expression of BMPR-IA, BMPR-IB, ActR-IIA and ActR-IIB was not affected. Culture with carnosine increased phosphorylation of Smad1, a signal-transducing molecule for BMP-2 and BMP-7. Noggin reduced carnosine-induced up-regulation of RUNX2/Cbfa1 and Sox9 mRNA, suggesting that BMPs were responsible for up-regulating RUNX2/Cbfa1 gene expression in human periodontal ligament cells.
  
  
  CONCLUSIONS
  These results suggest that carnosine enhance RUNX2/Cbfa1 and Sox9 expression of human periodontal ligament cells via the autocrine action of BMP-2 or BMP-7 produced by the cells.
authors.affiliation: Department of Biochemistry, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Ito-Kato
authors.forename: Naoto
authors.initials: N
authors.lastname: Suzuki
authors.forename: Masao
authors.initials: M
authors.lastname: Maeno
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takada
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tanabe
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Takayama
authors.forename: Koichi
authors.initials: K
authors.lastname: Ito
authors.forename: Kichibee
authors.initials: K
authors.lastname: Otsuka
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002336:Carnosine / Q000494:pharmacology*; D002352:Carrier Proteins; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D006609:High Mobility Group Proteins / Q000096:biosynthesis*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology; D055758:SOX9 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000502:physiology; D000099176:Noggin Protein
chemical_list: D000469:Alkaline Phosphatase; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002336:Carnosine; D002352:Carrier Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D055758:SOX9 Transcription Factor; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525718:BMP2 protein, human; C525819:BMP7 protein, human; C497399:SMAD1 protein, human; C527932:SOX9 protein, human