An Adiponectin Receptor Agonist Reduces Type 2 Diabetic Periodontitis
An Adiponectin Receptor Agonist Reduces Type 2 Diabetic Periodontitis
复制标题
脂联素受体激动剂可减少 2 型糖尿病牙周炎
DOI：
10.1177/0022034518818449
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发表时间：
2019-03-01
影响因子：
7.6
通讯作者：
Chen, J.
中科院分区：
文献类型：
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作者：
Wu, X.;Qiu, W.;Chen, J.
糖尿病患者的牙周炎发病率是非糖尿病患者的两倍，2型糖尿病（T2D）相关的牙周炎在许多情况下由于高血糖条件下骨细胞功能的改变和异常而严重。因此，开发一种有效的方法来阻止疾病进程，以及恢复和再生失去的牙槽骨以保留糖尿病患者的天然牙齿，是至关重要的。在本研究中，我们应用一种新发现的脂联素受体激动剂AdipoRon（APR）治疗糖尿病动物模型的实验性牙周炎，并阐明其潜在的分子机制。我们发现，当APR全身淬灭饮食诱导的肥胖（DIO）糖尿病小鼠的血糖水平时，由于我们的体外研究显示APR对破骨细胞分化的抑制作用，它显著减少了破骨细胞数量和牙槽骨丢失。APR还减少了炎症分子CC、趋化因子配体2和白细胞介素6在患病牙龈组织中的产生。另一方面，APR通过促进成骨分化和减少骨髓中促进干细胞迁移的基质细胞衍生因子1来促进牙槽骨再生。APR治疗脂联素（APN）基因敲除小鼠诱导的牙周炎也获得了相同的结果，表明APR能够激活内源性APN受体发挥骨合成代谢作用。总之，我们的研究支持APR可用作靶向T2D相关牙周炎的有效多管齐下的方法的概念。
Periodontitis is twice as prevalent in diabetics as in nondiabetics, and type 2 diabetes (T2D)-associated periodontitis is severe in many cases due to the altered and aberrant functions of bone cells in hyperglycemic conditions. Therefore, developing an effective method to halt the disease process, as well as restore and regenerate lost alveolar bone to reserve the natural teeth in diabetics, is critically important. In the current study, we applied a newly discovered adiponectin receptor agonist AdipoRon (APR) in experimental periodontitis in diabetic animal models and demonstrated the underlying molecular mechanisms. We found that when APR systemically quenched the blood sugar level in diet-induced obesity (DIO) diabetic mice, it reduced osteoclast numbers and alveolar bone loss significantly due to APR's inhibition on osteoclast differentiation shown in our in vitro studies. APR also decreased the production of proinflammatory molecules CC chemokine ligand 2 and interleukin 6 in diseased gingival tissues. On the other hand, APR promoted alveolar bone regeneration through enhancing osteogenic differentiation and decreasing stromal cell-derived factor 1 in the bone marrow that facilitates stem cell migration. Same results were achieved by APR treatment of periodontitis induced in adiponectin (APN) knockout mice, indicating the ability of APR to activate the endogenous APN receptors to exert osteoanabolic effects. In summary, our study supports the notion that APR could be used as an effective multipronged approach to target T2D-associated periodontitis.