title: Nanohydroxyapatite increases BMP-2 expression via a p38 MAP kinase dependent pathway in periodontal ligament cells.
abstract: OBJECTIVE
  Bone morphogenetic protein (BMP)-2 promotes the osteoblastic differentiation of human periodontal ligament (PDL) cells, which play a pivotal role in periodontal regeneration. Recently, nano-sized hydroxyapatite (nano-HA) has been highlighted due to its advantageous features over micro-sized materials.
  
  
  RESULTS
  We investigated the effect of nano-HA on BMP-2 expression in human PDL cells. Real time PCR analysis revealed that the expression of BMP-2 increased upon stimulation with nano-HA in dose- and time-dependent manners. An immunofluorescence assay demonstrated the synthesis of BMP-2 proteins. Concentrations of Ca(2+) as well as phosphate (Pi) in culture supernatants were unchanged, suggesting that nano-HA functioned as a nanoparticle rather than as a possible source for releasing Ca(2+) and/or Pi extracellularly, which were shown to also enhance the expression of BMP-2. Nano-HA-induced BMP-2 expression was dependent on the p38 MAP kinase pathway because increases in BMP-2 expression were inhibited by treatment with SB203580, a p38 inhibitor, and phosphorylation of p38 was detected by Western blotting.
  
  
  CONCLUSIONS
  This novel mechanism of nano-HA will be important for the rational design of future periodontal regeneration.
authors.affiliation: Division of Periodontology and Endodontology, Tohoku University, Graduate School of Dentistry, Sendai 980-8575, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Suto
authors.forename: Eiji
authors.initials: E
authors.lastname: Nemoto
authors.forename: Sousuke
authors.initials: S
authors.lastname: Kanaya
authors.forename: Risako
authors.initials: R
authors.lastname: Suzuki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Shimauchi
mesh_terms: D000328:Adult; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000187:drug effects*; D002118:Calcium / Q000032:analysis; D018929:Cell Culture Techniques; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D017886:Durapatite / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D010710:Phosphates / Q000032:analysis; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007093:Imidazoles; D007211:Indoles; D010710:Phosphates; D011725:Pyridines; C007293:DAPI; D017886:Durapatite; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D002118:Calcium