The role of macrophages in the periodontal regeneration using Emdogain® gel

Background and Objective: Emdogain((R)) gel is clinically used as a periodontal regenerative material. However, the mechanism of the regeneration has not been completely elucidated. Although many studies have focused on the regenerative effect of Emdogain on connective tissue attachment and alveolar bone, the role of macrophages and the expression of growth factors remains unclear in the regeneration stimulated by Emdogain gel in vivo. The aim of this study was to investigate the effect of Emdogain gel on the expression of cytokines and growth factors by macrophages in vivo using a newly devised rat experimental periodontitis model. Material and Methods: Rat experimental periodontitis was induced by elevating a full-thickness gingival flap and ligating silk threads around the first molars of the mandible. At 14 d after inducing experimental periodontitis, Emdogain gel or propylene glycol alginate was applied to the furcation area. The rats were killed 7 and 14 d after treatment with propylene glycol alginate or Emdogain gel. The expression of cytokines and growth factors, and the regeneration of periodontal tissue, were examined by histochemical and immunohistochemical methods. Results: Fourteen days after the induction of periodontitis, the resorption of alveolar bone at furcation was observed and cytokines such as interleukin-1 beta, transforming growth factor-beta 1, receptor activator of nuclear factor-kappa B ligand, receptor activator of nuclear factor-kappa B and osteoprotegerin were found. In the Emdogain-treatment group, the formation of new acellular cementum and, more remarkably, recovery of the bone, were observed. The new bone formation ratio in the Emdogain treatment group was significantly higher than that of the propylene glycol alginate treatment group. Although the expression of cytokines such as interleukin-1 beta, transforming growth factor-beta 1, receptor activator of nuclear factor-kappa B ligand and receptor activator of nuclear factor-kappa B was very low, bone morphogenetic protein-2- and bone morphogenetic protein-4-expressing macrophages were observed close to the root, and bone morphogenetic protein-4-expressing macrophages were mainly observed close to the bone surface at the furcation in the Emdogain-treatment group. Conclusion: These results suggest that wound-healing macrophages may express bone morphogenetic protein and play an important role in the regeneration of periodontal tissue at the furcation following the application of Emdogain gel.