The Effect Of Inhibition Of MMP 2 And 9 On The Rat Dentine-Pulp Complex

The mineralisation of predentine to dentine involves the modification of the extracellular matrix (ECM) prior to mineral deposition. Matrix metalloproteinases (MMPs) are a family of endopeptidases that are fundamental to a range of physiological and pathological processes, including dentinogenesis. Objective: The aim of this study was to examine the effect of inhibiting MMP 2 and 9 (gelatinases) on the dentine-pulp complex in vitro. Methods: 2-3mm slices were cut from Wistar rat incisors and cultured at the gas-liquid interface. Agarose beads soaked in MMP 2/9 inhibitor (Calbiochem) at a final concentration of 17nM or 30 nM, or 1.7µM MMP 2 inhibitor (Calbiochem) were carefully placed adjacent to the dentine-pulp interface. Beads soaked in the inhibitor diluent were used as controls. The sections were cultured for up to 14 days, fixed and processed for histological evaluation and predentine width measurement and statistical analysis. Results: Culture of incisor sections in the presence of MMP 2 and MMP 2/9 inhibitors resulted in the accumulation of ECM around and below the bead. When predentine widths were analysed, there was a statistically significant increase in predentine width in the MMP 2 inhibitor group at 14 days (p=0.0002) and in the 17 nM MMP 2/9 inhibitor group at 14 days (p< 0.0001) and at 7 and 14 days in the 30 nM MMP 2/9 inhibitor groups (p=0.0006 and p<0.0001 respectively). Conclusions: These studies demonstrate that MMPs are key to the normal turnover of the ECM in the dentine pulp complex and are also requisite for the turnover of predentine matrices as a prelude to mineral deposition.