Department of Medical Sciences, University of Trieste, Trieste, Italy.
Institute of Dentistry, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
J Dent Res. 2015 Feb;94(2):241-51. doi: 10.1177/0022034514562833. Epub 2014 Dec 22.
Dentin can be described as a biological composite with collagen matrix embedded with nanosized hydroxyapatite mineral crystallites. Matrix metalloproteinases (MMPs) and cysteine cathepsins are families of endopeptidases. Enzymes of both families are present in dentin and collectively capable of degrading virtually all extracellular matrix components. This review describes these enzymes and their presence in dentin, mainly focusing on their role in dentin caries pathogenesis and loss of collagen in the adhesive hybrid layer under composite restorations. MMPs and cysteine cathepsins present in saliva, mineralized dentin, and/or dentinal fluid may affect the dentin caries process at the early phases of demineralization. Changes in collagen and noncollagenous protein structure may participate in observed decreases in mechanical properties of caries-affected dentin and reduce the ability of caries-affected dentin to remineralize. These endogenous enzymes also remain entrapped within the hybrid layer during the resin infiltration process, and the acidic bonding agents themselves (irrespective of whether they are etch-and-rinse or self-etch) can activate these endogenous protease proforms. Since resin impregnation is frequently incomplete, denuded collagen matrices associated with free water (which serves as a collagen cleavage reagent for these endogenous hydrolase enzymes) can be enzymatically disrupted, finally contributing to the degradation of the hybrid layer. There are multiple in vitro and in vivo reports showing that the longevity of the adhesive interface is increased when nonspecific enzyme-inhibiting strategies are used. Different chemicals (i.e., chlorhexidine, galardin, and benzalkonium chloride) or collagen cross-linker agents have been successfully employed as therapeutic primers in the bonding procedure. In addition, the incorporation of enzyme inhibitors (i.e., quaternary ammonium methacrylates) into the resin blends has been recently promoted. This review will describe MMP functions in caries and hybrid layer degradation and explore the potential therapeutic role of MMP inhibitors for the development of improved intervention strategies for MMP-related oral diseases.
牙本质可被描述为一种生物复合材料，其中胶原基质中嵌入有纳米级羟磷灰石矿物质微晶。基质金属蛋白酶（MMPs）和半胱氨酸蛋白酶属于内肽酶家族。这两个家族的酶都存在于牙本质中，它们共同能够降解几乎所有细胞外基质成分。本综述描述了这些酶及其在牙本质中的存在，主要侧重于它们在牙本质龋发病机制以及复合树脂修复体下黏合混合层中胶原丢失中的作用。唾液、矿化牙本质和/或牙本质液中的 MMPs 和半胱氨酸蛋白酶可能会影响脱矿早期的牙本质龋进程。胶原和非胶原蛋白结构的变化可能会参与观察到的龋病牙本质力学性能下降，并降低龋病牙本质的再矿化能力。这些内源性酶也在树脂渗透过程中被捕获在混合层内，而酸性黏结剂本身（无论它们是酸蚀-冲洗还是自酸蚀）都可以激活这些内源性蛋白酶原。由于树脂浸渍通常不完整，与自由水相关的无覆盖胶原基质（其作为这些内源性水解酶的胶原裂解试剂）可以被酶促破坏，最终导致混合层降解。有多项体外和体内报告表明，使用非特异性酶抑制策略可以提高黏附界面的耐久性。已经成功地将多种化学物质（即洗必泰、加兰他敏和苯扎氯铵）或胶原交联剂用作黏接程序中的治疗性底漆。此外，最近还提倡将酶抑制剂（即季铵甲基丙烯酸酯）掺入树脂混合物中。本综述将描述 MMP 在龋病和混合层降解中的作用，并探讨 MMP 抑制剂在开发改善 MMP 相关口腔疾病的干预策略方面的潜在治疗作用。
