title: Interactions of regenerative, inflammatory and biomechanical signals on bone morphogenetic protein-2 in periodontal ligament cells.
abstract: OBJECTIVE
  Regeneration of periodontal tissues by EMD remains a major challenge because a number of modifying factors are as yet unknown. The effects of EMD seem to be mediated, at least in part, by bone morphogenetic protein-2 (BMP-2). This in vitro study was performed to examine whether the effects of EMD on BMP-2 activity are modulated by inflammatory and/or biomechanical signals.
  
  
  METHODS
  Periodontal ligament cells were seeded on BioFlex(®) plates and exposed to EMD under normal, inflammatory or biomechanical loading conditions for 1 and 6 d. In order to mimic proinflammatory or biomechanical loading conditions in vitro, cells were stimulated with interleukin-1β (IL-1β), which is increased at inflamed periodontal sites, and cyclic tensile strain of various magnitudes, respectively. The synthesis of BMP-2, its receptors (BMPR-1A, BMPR-1B and BMPR-2) and its inhibitors (follistatin, matrix gla protein and noggin) were analyzed using real-time RT-PCR and ELISA.
  
  
  RESULTS
  In EMD-treated cells, BMP-2 synthesis was increased significantly at 1 d. EMD also induced the expression of all BMP receptors, and of the BMP inhibitors follistatin and noggin. In general, IL-1β and biomechanical loading neither down-regulated BMP-2 nor up-regulated BMP inhibitors in EMD-stimulated cells. However, IL-1β and biomechanical loading, when applied for a longer time period, caused a down-regulation of EMD-induced BMP receptors.
  
  
  CONCLUSIONS
  EMD induces not only BMP-2, but also its receptors and inhibitors, in PDL cells. IL-1β and biomechanical forces may counteract the beneficial effects of EMD on BMP-2 activity via the down-regulation of BMP receptors.
authors.affiliation: Clinical Research Unit, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Nokhbehsaim
authors.forename: B
authors.initials: B
authors.lastname: Deschner
authors.forename: J
authors.initials: J
authors.lastname: Winter
authors.forename: C
authors.initials: C
authors.lastname: Bourauel
authors.forename: B
authors.initials: B
authors.lastname: Rath
authors.forename: A
authors.initials: A
authors.lastname: Jäger
authors.forename: S
authors.initials: S
authors.lastname: Jepsen
authors.forename: J
authors.initials: J
authors.lastname: Deschner
mesh_terms: D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000187:drug effects; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000187:drug effects; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D038681:Follistatin / Q000494:pharmacology; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology / Q000201:enzymology*; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical; D013997:Time Factors; D000097568:Matrix Gla Protein; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D003746:Dental Enamel Proteins; D016326:Extracellular Matrix Proteins; D038681:Follistatin; D053583:Interleukin-1beta; D000097568:Matrix Gla Protein; D000099176:Noggin Protein; C525718:BMP2 protein, human; C109069:enamel matrix proteins; C498218:BMPR2 protein, human