The dynamics of TGF-β in dental pulp, odontoblasts and dentin

Transforming growth factor-beta (TGF-beta) is critical for cell proliferation and differentiation in dental pulp. Here, we show the dynamic mechanisms of TGF-beta in porcine dental pulp, odontoblasts and dentin. The mRNA of latent TGF-beta 1 and TGF-beta 3 is predominantly expressed in odontoblasts, whereas the mRNA expression level of latent TGF-2 is high in dental pulp. TGF-beta 1 is a major isoform of TGF-beta, and latent TGF-beta 1, synthesized in dental pulp, is primarily activated by matrix metalloproteinase 11 (MMP11). Activated TGF-beta 1 enhances the mRNA expression levels of MMP20 and full-length dentin sialophosphoprotein (DSPP) in dental pulp cells, coinciding with the induction of odontoblast differentiation. Latent TGF-beta 1 synthesized in odontoblasts is primarily activated by MMP2 and MMP20 in both odontoblasts and dentin. The activity level of TGF-beta 1 was reduced in the dentin of MMP20 null mice, although the amount of latent TGF-beta 1 expression did not change between wild-type and MMP20 null mice. TGF-beta 1 activity was reduced with the degradation of DSPP-derived proteins that occurs with ageing. We propose that to exert its multiple biological functions, TGF-beta 1 is involved in a complicated dynamic interaction with matrix metalloproteinases (MMPs) and/or DSPP-derived proteins present in dental pulp, odontoblasts and dentin.