Interactions of regenerative, inflammatory and biomechanical signals on bone morphogenetic protein-2 in periodontal ligament cells

J Periodontal Res. 2011 Jun;46(3):374-81. doi: 10.1111/j.1600-0765.2011.01357.x. Epub 2011 Mar 17.

Abstract

Background and 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.

Material and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomechanical Phenomena
  • Bone Morphogenetic Protein 2 / antagonists & inhibitors
  • Bone Morphogenetic Protein 2 / drug effects
  • Bone Morphogenetic Protein 2 / physiology*
  • Bone Morphogenetic Protein Receptors, Type I / drug effects
  • Bone Morphogenetic Protein Receptors, Type II / drug effects
  • Bone Morphogenetic Proteins / antagonists & inhibitors
  • Calcium-Binding Proteins / pharmacology
  • Carrier Proteins / pharmacology
  • Cells, Cultured
  • Dental Enamel Proteins / pharmacology*
  • Extracellular Matrix Proteins / pharmacology
  • Follistatin / pharmacology
  • Humans
  • Inflammation
  • Interleukin-1beta / pharmacology
  • Matrix Gla Protein
  • Osteogenesis / drug effects
  • Periodontal Ligament / cytology
  • Periodontal Ligament / enzymology*
  • Regeneration / physiology
  • Signal Transduction / drug effects
  • Stress, Mechanical
  • Time Factors

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Calcium-Binding Proteins
  • Carrier Proteins
  • Dental Enamel Proteins
  • Extracellular Matrix Proteins
  • Follistatin
  • Interleukin-1beta
  • enamel matrix proteins
  • noggin protein
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type I
  • Bone Morphogenetic Protein Receptors, Type II