The effects of MMP inhibitors on human salivary MMP activity and caries progression in rats
The effects of MMP inhibitors on human salivary MMP activity and caries progression in rats
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DOI：
10.1177/00220345010800061301
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发表时间：
2001-06-01
影响因子：
7.6
通讯作者：
Tjäderhane, L
中科院分区：
文献类型：
--
作者：
Sulkala, M;Wahlgren, J;Tjäderhane, L
以往的研究表明，唾液和牙髓来源的宿主酶--基质金属蛋白酶(MMPs)可能参与牙本质龋病的发生。为了研究非抗菌化学修饰的四环素(CMTs)对酸激活的人唾液MMPs的抑制作用，我们采用了以I-125标记的明胶为底物的功能活性测定方法。为了阐明MMPs在体内裂隙龋病进展中的作用，我们给年轻大鼠口服基质金属蛋白酶抑制剂CMT-3和唑来膦酸盐，每周5天，共7周。采用Schiff试剂对下颌磨牙矢状面的龋损进行显影。CMT-3可显著降低人唾液MMPs的明胶溶解活性。CMT-3和唑来膦酸盐单独和联合使用，也可以减少大鼠牙本质龋齿的进展。这些结果表明，MMPs在牙本质龋病发病机制中起着重要作用，MMPs抑制剂可能被证明在预防龋病进展中是有用的。
Previous studies suggest that salivary and pulp-derived host enzymes, matrix metalloproteinases (MMPs), may be involved in dentin caries pathogenesis. To study the inhibition of acid-activated human salivary MMPs by non-antimicrobial chemically modified tetracyclines (CMTs), we used a functional activity 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 MMP inhibitors CMT-3 and zoledronate to young rats per os for 7 weeks, 5 days a week. Caries lesions were visualized by Schiff reagent in sagittally sectioned mandibular molars. Marked reduction in gelatinolytic activity of human salivary MMPs was observed with CMT-3. CMT-3 and zoledronate, both alone and in combination, also reduced dentin caries progression in the rats. These results suggest that MMPs have an important role in dentin caries pathogenesis, and that MMP inhibitors may prove to be useful in the prevention of caries progression.