The effects of MMP inhibitors on human salivary MMP activity and caries progression in rats

Previous studies suggest that salivary and pulp-derived host enzymes, matri x metalloproteinases (MMPs), may be involved in dentin caries pathogenesis. To study the inhibition of acid-activated human salivary MMPs by non-antim icrobial chemically modified tetracyclines (CMTs), we used a functional act ivity assay with I-125-labeled gelatin as a substrate. To address the role of MMPs in the progression of fissure caries in vivo, we administered the M MP inhibitors CMT-3 and zoledronate to young rats per os for 7 weeks, 5 day s a week. Caries lesions were visualized by Schiff reagent in sagittally se ctioned mandibular molars. Marked reduction in gelatinolytic activity of hu man salivary MMPs was observed with CMT-3. CMT-3 and zoledronate, both alon e and in combination, also reduced dentin caries progression in the rats. T hese results suggest that MMPs have an important role in dentin caries path ogenesis, and that MMP inhibitors may prove to be useful in the prevention of caries progression.