| Summary: | Previous studies have reported that the adult periodontal ligament (PDL) may contain progenitor/stem cells that function as precursors for periodontal tissue regeneration, although the ability of this population to differentiate into the multiple lineages present in the PDL is not yet certain. In addition, although Enamel Matrix Derivative (EMD; Emdogain®), derived from the enamel matrix of developing teeth) has been used extensively to help re-build new periodontal tissue, its effect on bone regeneration remains inconclusive and its effect on PDL blood vessels and nerve cell development not yet known, because it comprises a heterogeneous mixture of proteins. EMD has recently been separated into two main fractions: Fraction C, containing proteins < 6 kDa (mainly the tyrosine-rich amelogenin peptide TRAP); and Fraction A, containing proteins > 6 KDa (including the full-length amelogenin, sheathlins and a leucine-rich amelogenin peptide LRAP). The present study examined the effects of EMD Fractions on multi-lineage differentiation pathays of PDL cells in vitro. The results of the present study have shown that that Fraction C and Fraction A differentially regulate multilineage specification of PDL cells. Thus, Fraction C was found to up-regulate chondrogenic, vasculogenic, angiogenic, neurogenic and gliogenic genes and ‘terminal’ differentiation, whereas Fraction A was found to stimulate osteogenic genes and terminal osteogenic differentiation in vitro; both fractions suppressed adipogenesis. Moreover, the TRAP and LRAP peptides of Fraction C and Fraction A, respectively, were found to be at least partly responsible for the differential activities of these two fractions. In addition, at least some components in these EMD Fractions bound to and were internalized into PDL cells, most probably by receptor-mediated endocytosis. These findings thus demonstrate that the PDL contains cells with multi-lineage differentiation potential and that the components of EMD have differential effects on the diverse activities on the heterogeneous cells present in the PDL.
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