Periodontal regenerative effect of enamel matrix derivative in diabetes.
Periodontal regenerative effect of enamel matrix derivative in diabetes.
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DOI：
10.1371/journal.pone.0207201
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Izumi Y
中科院分区：
文献类型：
--
作者：
Takeda K;Mizutani K;Matsuura T;Kido D;Mikami R;Noda M;Buranasin P;Sasaki Y;Izumi Y
本研究旨在探讨釉基质衍生物（EMD）对糖尿病患者牙周组织的再生作用。36只大鼠被分配到链脲佐菌素诱导的糖尿病或对照（非糖尿病）组。在双侧上颌磨牙中手术产生三壁骨内缺损，然后应用EMD或生理盐水。通过组织形态学分析和显微计算机断层扫描评价了原发性伤口闭合和缺损填充。通过实时聚合酶链反应定量缺损中炎症和血管生成因子的mRNA表达水平。从对照动物中分离牙龈成纤维细胞，并在高糖（HG）或对照培养基中培养。观察EMD对胰岛素抵抗及PI 3 K/Akt/VEGF信号通路的影响。在糖尿病和非糖尿病大鼠中，EMD治疗部位的一期闭合率和缺损填充参数显著高于EMD未治疗部位，尽管在双向重复测量方差分析中，糖尿病组的缺损填充显著低于对照组（两者均为p<0.05）。糖尿病大鼠经EMD处理的部位新形成的骨和牙骨质比对照组大鼠未经EMD处理的部位显著增加（两者均为p<0.05）。VEGF在糖尿病和非糖尿病大鼠的EMD治疗部位显著上调（对于两者，p<0.05）。在体外，胰岛素或EMD诱导的Akt磷酸化在HG培养基中培养的细胞中显著较低（p<0.05）。EMD介导的VEGF上调被Akt抑制剂渥曼青霉素抑制，尽管在HG培养基中效果显著较低（p<0.01）。总之，EMD可能通过Akt/VEGF信号促进牙周组织再生，即使在糖尿病条件下。
The present study aimed to investigate the periodontal regenerative effect of enamel matrix derivative (EMD) in diabetes. Thirty-six rats were assigned to streptozotocin-induced diabetes or control (non-diabetic) groups. Three-wall intrabony defects were surgically generated in the bilateral maxilla molar, followed by application of EMD or saline. Primary wound closure and defect fill were evaluated via histomorphological analysis and micro-computed tomography. mRNA expression levels of inflammatory and angiogenic factors in the defects were quantified via real-time polymerase chain reaction. Gingival fibroblasts were isolated from control animals and cultured in high-glucose (HG) or control medium. The effects of EMD on insulin resistance and PI3K/Akt/VEGF signaling were evaluated. The achievement rate of primary closure and the parameters of defect fill were significantly higher at EMD-treated site than at EMD-untreated sites in both diabetic and non-diabetic rats, although defect fill in the diabetic groups was significantly lower in the control groups on two-way repeated-measures analysis of variance (for both, p<0.05). Newly formed bone and cementum were significantly increased at EMD-treated sites in diabetic rats than at EMD-untreated sites in control rats (for both, p<0.05). Vegf was significantly upregulated at EMD-treated sites in both diabetic and non-diabetic rats (for both, p<0.05). In vitro, insulin or EMD-induced Akt phosphorylation was significantly lower in cells cultured in HG medium (p<0.05). EMD-mediated Vegf upregulation was suppressed by the Akt inhibitor wortmannin, although the effect was significantly lower in HG medium (p<0.01). In conclusion, EMD might promote periodontal tissue regeneration via Akt/VEGF signaling, even in a diabetic condition.