Abstract
Transforming growth factor-beta (TGF-β) is critical for cell proliferation and differentiation in dental pulp. Here, we show the dynamic mechanisms of TGF-β in porcine dental pulp, odontoblasts and dentin. The mRNA of latent TGF-β1 and TGF-β3 is predominantly expressed in odontoblasts, whereas the mRNA expression level of latent TGF-β2 is high in dental pulp. TGF-β1 is a major isoform of TGF-β, and latent TGF-β1, synthesized in dental pulp, is primarily activated by matrix metalloproteinase 11 (MMP11). Activated TGF-β1 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-β1 synthesized in odontoblasts is primarily activated by MMP2 and MMP20 in both odontoblasts and dentin. The activity level of TGF-β1 was reduced in the dentin of MMP20 null mice, although the amount of latent TGF-β1 expression did not change between wild-type and MMP20 null mice. TGF-β1 activity was reduced with the degradation of DSPP-derived proteins that occurs with ageing. We propose that to exert its multiple biological functions, TGF-β1 is involved in a complicated dynamic interaction with matrix metalloproteinases (MMPs) and/or DSPP-derived proteins present in dental pulp, odontoblasts and dentin.
Highlights
Transforming growth factor-beta (TGF-β) is a signalling molecule that induces cell proliferation, cell differentiation, chemotaxis and apoptosis in monocytes and epithelial, mesenchymal and neuronal cells[1]
Using Quantitative real-time PCR (qPCR), primer sets that we designed and total RNA isolated from pulp tip (PT), pulp body (PB), and OD (Fig. 1b), we quantified the mRNA expression levels of TGF-β receptor type I (TGFBR1), bone morphogenetic protein 1 (BMP1), inactive TGF-βs, active TGF-βs, and matrix metalloproteases (MMPs)
The mRNA expression levels of MMP2 (Fig. 1k) and MMP20 (Fig. 1l) were predominantly increased in OD, whereas matrix metalloproteinase 11 (MMP11) mRNA expression was high in PT and PB, with only trace expression detected in OD (Fig. 1m)
Summary
Transforming growth factor-beta (TGF-β) is a signalling molecule that induces cell proliferation, cell differentiation, chemotaxis and apoptosis in monocytes and epithelial, mesenchymal and neuronal cells[1]. Activation of TGF-β is induced by pH13, reactive oxygen species[14], thrombospondin-115 and integrins[16,17,18,19] Proteases such as plasmin and matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, activate TGF-β through proteolytic degradation of the latent TGF-β complex[20,21]. The activation mechanism of TGF-β, the roles of activated TGF-β in dental pulp and odontoblasts, and the inactivation mechanism of TGF-β in dentin matrix are still unclear. We measured the gene expression of TGF-β and its associated MMPs, activation of TGF-β by the MMPs, TGF-β signal induction in odontoblast differentiation, and changes in the amount of DSPP-derived proteins and TGF-β activity with ageing at both the protein and genetic levels
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