Identification creation of bioactive sites of enamel proteins for developing a new therapy of periodontal tissue regeneration.

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To identify the bioactive components and sites in Emdogain (EMD), which is widely used as a periodontal regenerative therapy, and to explore the possibility of developing new medicament using the synthetic peptide of the active sites for periodontal tissue regeneration, we achieved the following studies. 1.Cellular and molecular mechanism of stimulative effects of EMD on proliferation and differentiation of periodontal cells such as periodontal ligament cells (PDLC), gingival epithelial cells, gingival fibroblasts and osteoblasts. 2.Signal pathways and receptors of EMD, 3.Determination of active components and sites of EMD, and 4.Effects of the synthetic peptide of the active site on PDLC proliferation and differentiation in vitro and periodontal tissue regeneration in vivo. The results of the studies were 1.EMD stimulated proliferation and differentiation of PDLC and osteoblasts and inhibited those of gingival epithelial cells and fibroblasts, 2.RTK-ERK 1/2 pathway was possibly involved in mitogenic response of PDLC to EMD, 3.An anti-ameloblastin antibody suppressed stimulatory effects of EMD on PDLC proliferation and differentiation, and 4.The synthetic peptide of the active site of ameloblastin stimulated proliferation and differentiation of PDLC and periodontal tissue regeneration. In conclusions, EMD has suitable bioactivities to periodontal tissue regeneration and the synthetic peptide determined in the present study could be used as a new periodontal tissue regeneration therapy.