Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice.
Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice.
复制标题
高血糖和口干症是 1 型糖尿病小鼠蛀牙的关键决定因素。
DOI：
10.1038/labinvest.2012.60
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发表时间：
2012-06
期刊：
影响因子：
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通讯作者：
Abboud-Werner S
中科院分区：
文献类型：
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作者：
Yeh CK;Harris SE;Mohan S;Horn D;Fajardo R;Chun YH;Jorgensen J;Macdougall M;Abboud-Werner S
胰岛素依赖型1型糖尿病（DM）与口腔疾病密切相关。糖尿病患者代谢控制不良与牙龈炎、牙周炎和牙齿脱落的高风险相关。糖尿病患者和口干患者的唾液流量下降。唾液减少易导致牙釉质矿化不足和龋齿形成;然而，1型糖尿病引发和导致蛀牙和牙周炎进展的机制尚未探讨。为了解决这个问题，我们分析了秋田−/−小鼠的牙齿形态，这些小鼠在Ins 2胰岛素基因中存在点突变，导致进行性高血糖。通过microCT、扫描电镜和组织学分析秋田-/-和野生型同窝仔的下颌骨;检查牙齿的釉原蛋白（Amel）和成釉蛋白（Ambn）表达。给小鼠注射毛果芸香碱以评估唾液产生。由于高血糖可能改变牙髓修复，因此还分析了高葡萄糖水平对培养的MD 10-F2牙髓细胞增殖/分化的影响。结果显示，6周龄的秋田−/−小鼠表现出白垩白色门牙，这与明显的高血糖和唾液分泌受损有关。秋田−/−牙齿的MicroCT显示釉质过度磨损和矿化不足; Amel和Ambn的免疫染色减少。一个显著的特点是牙本质小管的侵袭与缓症链球菌和微脓肿，起源于冠髓和发展为牙髓坏死和根尖周炎。高浓度葡萄糖也抑制MD 10-F2细胞的增殖和分化。我们的研究结果提供了第一个证据表明，在1型糖尿病模型中，高血糖症与唾液减少相结合会导致釉质矿化/基质蛋白减少，并容易导致过度磨损和腐烂。重要的是，高血糖症对釉质基质蛋白和牙髓修复产生不利影响。早期发现和治疗高血糖和低唾液分泌可能为预防糖尿病的牙科并发症和促进口腔健康提供一个有用的策略。
Insulin-dependent type 1 diabetes mellitus (DM) and oral diseases are closely interrelated. Poor metabolic control in diabetics is associated with a high risk of gingivitis, periodontitis and tooth loss. Salivary flow declines in diabetics and patients suffer from xerostomia. Reduced saliva predisposes to enamel hypomineralization and caries formation; however, the mechanisms that initiate and lead to progression of tooth decay and periodontitis in type 1 DM have not been explored. To address this issue, we analyzed tooth morphology in Akita −/− mice that harbor a point mutation in the Ins2 insulin gene, which leads to progressive hyperglycemia. Mandibles from Akita −/− and wild-type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin (Amel) and ameloblastin (Ambn) expression. Mice were injected with pilocarpine to assess saliva production. As hyperglycemia may alter pulp repair, the effect of high glucose levels on the proliferation/differentiation of cultured MD10-F2 pulp cells was also analyzed. Results showed that Akita −/− mice at 6 weeks of age showed chalky white incisors that correlated with marked hyperglycemia and impaired saliva production. MicroCT of Akita −/− teeth revealed excessive enamel wearing and hypomineralization; immunostaining for Amel and Ambn was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in the coronal pulp and progressed to pulp necrosis and periapical periodontitis. High levels of glucose also inhibited MD10-F2 cell proliferation and differentiation. Our findings provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type1 DM leads to decreased enamel mineralization/matrix proteins and predisposes to excessive wearing and decay. Importantly, hyperglycemia adversely affects enamel matrix proteins and pulp repair. Early detection and treatment of hyperglycemia and hyposalivation may provide a useful strategy for preventing the dental complications of diabetes and promoting oral health in this population.