Chloroquine and 3-Methyladenine Attenuates Periodontal Inflammation and Bone Loss in Experimental Periodontitis
Chloroquine and 3-Methyladenine Attenuates Periodontal Inflammation and Bone Loss in Experimental Periodontitis
复制标题
氯喹和3-甲基腺嘌呤减轻实验性牙周炎的牙周炎和骨丢失
DOI：
10.1007/s10753-019-01111-0
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发表时间：
2019-11-13
期刊：
影响因子：
5.1
通讯作者：
Yan, Fuhua
中科院分区：
文献类型：
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作者：
He, Shasha;Zhou, Qian;Yan, Fuhua
牙周炎是一种以骨稳态失衡引起的牙槽骨吸收为特征的炎症。自噬与炎症和骨代谢有关。然而，自噬抑制剂是否可以用于牙周炎的动物模型仍然未知。我们研究了两种经典的自噬抑制剂，3-甲基腺嘌呤（3-MA）和氯喹（CQ），在大鼠实验性牙周炎的发展中的作用，在骨丢失（micro-CT），炎症细胞的数量（苏木精和伊红染色），和骨细胞活性（抗酒石酸酸性磷酸酶染色）。免疫组化检测自噬相关基因和核因子κ B p65（NF-κ B p65）的表达。Western blot分析Beclin-1和微管相关蛋白1A/1B轻链3（LC 3）的表达。为了进一步观察自噬抑制剂对体外破骨细胞（OC）的影响，使用骨髓来源的单核巨噬细胞。总之，这些研究结果表明，局部施用3-MA或CQ减少实验性牙周炎中炎性细胞的浸润和牙槽骨吸收。此外，3-MA和CQ可以减弱自噬对OC的激活。因此，3 MA和CQ可能具有预防和治疗牙周炎炎症和牙槽骨吸收的潜力。
Periodontitis is an inflammation characterized by alveolar bone resorption caused by imbalance in bone homeostasis. It is known that autophagy is related to inflammation and bone metabolism. However, whether autophagy inhibitors could be used for periodontitis in animal models remains unknown. We investigated the role of two classical autophagy inhibitors, 3-methyladenine (3-MA) and chloroquine (CQ), on the development of rat experimental periodontitis in terms of the bone loss (micro-CT), the number of inflammatory cells (hematoxylin and eosin staining), and the osteoclastic activity (tartrate-resistant acid phosphatase staining). Expression of autophagy-related genes and nuclear factor kappa B p65 (NF-kappa B p65) were assessed by immunohistochemistry. Expression of Beclin-1 and microtubule-associated proteins 1A/1B light chain 3 (LC3) were analyzed by Western blot. To further observe the effect of autophagy inhibitors on osteoclasts (OCs) in vitro, bone marrow-derived mononuclear macrophages were used. Together, these findings indicated that topical administration of 3-MA or CQ reduced the infiltration of inflammatory cells and alveolar bone resorption in experimental periodontitis. Furthermore, 3-MA and CQ may attenuate activation of OCs by autophagy. Therefore, 3MA and CQ may have prophylactic and therapeutic potential for inflammation and alveolar bone resorption in periodontitis in the future.