RESUMO
Transforming growth factor-ß1 (TGF-ß1) is present in porcine enamel extracts and is critical for proper mineralization of tooth enamel. Here, we show that the mRNA of latent TGF-ß1 is expressed throughout amelogenesis. Latent TGF-ß1 is activated by matrix metalloproteinase 20 (MMP20), coinciding with amelogenin processing by the same proteinase. Activated TGF-ß1 binds to the major amelogenin cleavage products, particularly the neutral-soluble P103 amelogenin, to maintain its activity. The P103 amelogenin-TGF-ß1 complex binds to TGFBR1 to induce TGF-ß1 signalling. The P103 amelogenin-TGF-ß1 complex is slowly cleaved by kallikrein 4 (KLK4), which is secreted into the transition- and maturation-stage enamel matrix, thereby reducing TGF-ß1 activity. To exert the multiple biological functions of TGF-ß1 for amelogenesis, we propose that TGF-ß1 is activated or inactivated by MMP20 or KLK4 and that the amelogenin cleavage product is necessary for the in-solution mobility of TGF-ß1, which is necessary for binding to its receptor on ameloblasts and retention of its activity.
