Buduneli Eralp, Vardar-Şengül Saynur, Buduneli Nurcan, Atilla Gül, Wahlgren Jaana, Sorsa Timo
Department of Periodontology, School of Dentistry, Ege University, İzmir, Turkey.
University of Helsinki, Institute of Dentistry and Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki, Finland.
J Periodontol. 2007 Jan;78(1):127-134. doi: 10.1902/jop.2007.050451.
Matrix metalloproteinases (MMPs) play important roles in tissue destruction mechanisms of periodontitis. MMP-8 and -13 are the major collagenases that act in extracellular matrix degradation in periodontal tissues. MMP-14 is a membrane-type MMP, and laminin (Ln)-- is a basal membrane component. The aim of the present study was to evaluate the effects of doxycycline and alendronate on gingival tissue expression of MMP-8, -13, and -14; tissue inhibitors of MMP (TIMP)-1; and Ln-5 γ2 chain in experimental periodontitis induced by Escherichia coli endotoxin (LPS) in rats.
Experimental periodontitis was induced by repeated injection of LPS. Forty-four adult male Sprague-Dawley rats were divided into five study groups: saline control, LPS, LPS + doxycycline, LPS + alendronate, and LPS + doxycycline + alendronate. Doxycycline and alendronate were given as a single agent or as combination therapy during the 7 days of the experimental study period. On day 7, the rats were sacrificed, and the gingival tissues were analyzed immunohistochemically for expression of MMP-8, -13, and -14, Ln-- γ2 chain, and TIMP-1. Alveolar bone loss was evaluated morphometrically under a stereomicroscope. Data were tested statistically by Kruskal-Wallis and Mann-Whitney tests and Spearman correlation analysis.
Alveolar bone loss was significantly higher in the LPS, doxycycline, alendronate, and combination groups than in the saline control group (all P <0.01). MMP-8 expression was significantly higher in the LPS group than in the saline control group (P = 0.001). Individual administration of doxycycline or alendronate significantly decreased the expression of MMP-8 compared to LPS (P = 0.01). Combined drug administration reduced MMP-14 significantly compared to doxycycline (P = 0.004). No significant differences in Ln-5 γ2 chain expression were found between the study groups (P >0.05). MMP-14 significantly correlated with the Ln-5 γ2 chain in the LPS + alendronate group (P = 0.04) and with the amount of alveolar bone loss in the LPS + doxycycline + alendronate group (P = 0.03).
Our findings suggest that alendronate and/or doxycycline may inhibit MMP-8 expression significantly; particularly, their combined administration may provide beneficial effects in periodontal treatment. Moreover, individual administration of alendronate and doxycycline results in significant increases in TIMP-1 expression in gingiva. However, these effects of combined low-dose doxycycline and alendronate on MMPs and TIMP should be verified by clinical human trials before these agents are used in dental practice.
基质金属蛋白酶（MMPs）在牙周炎的组织破坏机制中起重要作用。MMP - 8和 - 13是在牙周组织细胞外基质降解中起作用的主要胶原酶。MMP - 14是一种膜型MMP，层粘连蛋白（Ln）是基底膜成分。本研究的目的是评估强力霉素和阿仑膦酸钠对大鼠大肠杆菌内毒素（LPS）诱导的实验性牙周炎中牙龈组织MMP - 8、 - 13和 - 14、MMP组织抑制剂（TIMP） - 1以及Ln - 5γ2链表达的影响。
通过反复注射LPS诱导实验性牙周炎。44只成年雄性Sprague - Dawley大鼠分为五个研究组：生理盐水对照组、LPS组、LPS + 强力霉素组、LPS + 阿仑膦酸钠组和LPS + 强力霉素 + 阿仑膦酸钠组。在实验研究期间的7天内，强力霉素和阿仑膦酸钠作为单一药物或联合治疗给药。在第7天，处死大鼠，对牙龈组织进行免疫组织化学分析，以检测MMP - 8、 - 13和 - 14、Ln - γ2链以及TIMP - 1的表达。在体视显微镜下形态计量评估牙槽骨吸收情况。数据通过Kruskal - Wallis检验、Mann - Whitney检验和Spearman相关性分析进行统计学检验。
LPS组、强力霉素组、阿仑膦酸钠组和联合用药组的牙槽骨吸收明显高于生理盐水对照组（均P <0.01）。LPS组MMP - 8表达明显高于生理盐水对照组（P = 0.001）。与LPS组相比，单独给予强力霉素或阿仑膦酸钠可显著降低MMP - 8的表达（P = 0.01）。联合用药与强力霉素组相比，显著降低了MMP - 14的表达（P = 0.004）。各研究组之间Ln - 5γ2链表达无显著差异（P >0.05）。在LPS + 阿仑膦酸钠组中，MMP - 14与Ln - 5γ2链显著相关（P = 0.04），在LPS + 强力霉素 + 阿仑膦酸钠组中，MMP - 14与牙槽骨吸收量显著相关（P = 0.03）。
我们的研究结果表明，阿仑膦酸钠和/或强力霉素可能显著抑制MMP - 8的表达；特别是，它们联合给药可能在牙周治疗中产生有益效果。此外，单独给予阿仑膦酸钠和强力霉素可导致牙龈中TIMP - 1表达显著增加。然而，在这些药物用于牙科实践之前，联合低剂量强力霉素和阿仑膦酸钠对MMPs和TIMP的这些作用应通过临床人体试验进行验证。
