Interactions of Enamel Matrix Derivative and Biomechanical Loading in Periodontal Regenerative Healing

Background: Although enamel matrix derivative (EMD) has been shown to promote periodontal regeneration, it is unknown whether the actions of EMD are modulated by occlusal loading. This in vitro study was performed to investigate whether biomechanical forces regulate the response of periodontal ligament (PDL) cells to EMD. Methods: Human PDL cells were treated with EMD in the presence and absence of cyclic tensile strain (CTS) of various magnitudes for <= 14 days. Synthesis of transforming growth factor (TGF)-beta 1, vascular endothelial growth factor (VEGF), growth factor receptors, collagen, and runt-related transcription factor 2- (RUNX2), cell numbers and adhesion, wound fill rate, and calcium accumulation were analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, a wound healing assay, and alizarine red S staining. Results: Wound fill rate, cell numbers and adhesion, and expression of TGF-beta 1, VEGF, collagen, and RUNX2 were significantly increased by EMD. In the presence of CTS, the EMD-induced effects were significantly reduced. The inhibition of the EMD-upregulated VEGF expression by CTS was blocked by a specific inhibitor of nuclear factor-kappa B signaling. Moreover, CTS downregulated receptors for growth factors involved in the actions of EMD. CTS also antagonized significantly the EMD-induced calcium deposition. Conclusions: These in vitro findings suggest that the beneficial actions of EMD on PDL cell functions critical for periodontal regeneration are jeopardized by biomechanical loading. Clinical studies should clarify whether protection of teeth against occlusal forces in the early healing stage may positively affect the outcome of regenerative therapy with EMD. J Periodontol 2011;82:1725-1734.