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

Nokhbehsaim M, Deschner B, Winter J, Bourauel C, Rath B, Jäger A, Jepsen S, Deschner J. Interactions of regenerative, inflammatory and biomechanical signals on bone morphogenetic protein‐2 in periodontal ligament cells. J Periodont Res 2011; 46: 374–381.© 2011 John Wiley & Sons A/S 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.