Antimicrobial function of the polyunsaturated fatty acid KetoC in an experimental model of periodontitis
Antimicrobial function of the polyunsaturated fatty acid KetoC in an experimental model of periodontitis
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DOI：
10.1002/jper.19-0130
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发表时间：
2019-09-12
影响因子：
4.3
通讯作者：
Yamazaki, Kazuhisa
中科院分区：
文献类型：
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作者：
Sulijaya, Benso;Yamada-Hara, Miki;Yamazaki, Kazuhisa
背景 由肠道细菌产生的生物活性代谢物 KetoC 具有多种有益作用。然而，其在牙周炎发病机制中的作用仍不清楚。在这里，我们研究了 KetoC 在小鼠牙周炎模型中的作用，并探讨了其潜在机制。方法将 31 只 8 周龄雄性 C57BL/6N 小鼠随机分为 4 组（未结扎、未结扎 + KetoC、结扎 + 牙龈卟啉单胞菌和结扎 + 牙龈卟啉单胞菌 + KetoC）（n = 7/8 小鼠/组），每天口服 KetoC (15 mg/mL) 或载体，持续 2 周。为了诱发牙周炎，第7天在上颌左侧第二磨牙上放置5-0丝结扎线，每3天口服牙龈卟啉单胞菌W83（10（9）菌落形成单位[CFU]）。第14天，所有小鼠均被安乐死。牙槽骨破坏是根据牙骨质-牙釉质连接处到牙槽骨嵴的水平来确定的。此外，通过用苏木精和伊红染色的牙龈组织切片来确认骨质流失水平。使用实时聚合酶链式反应对牙龈卟啉单胞菌的存在进行定量。在体外，通过分析其对牙龈卟啉单胞菌增殖的抑制活性并使用活/死细菌染色试剂盒分别评估KetoC的抑菌和杀菌作用。然后使用双键缺陷代谢物 (KetoB) 研究双键结构在 KetoC 对牙龈卟啉单胞菌抗菌活性中的重要性。结果在体内，KetoC 可减轻牙槽骨破坏并抑制牙周炎组中的牙龈卟啉单胞菌。在体外，KetoC（但不是 KetoB）以剂量依赖性方式下调牙龈卟啉单胞菌的增殖和活力。结论 KetoC 通过其抗菌功能减少牙周炎模型中的牙槽骨破坏。因此，这种生物活性代谢物在支持牙周治疗的临床应用中可能有价值。
Background The bioactive metabolite KetoC, generated by intestinal bacteria, exerts various beneficial effects. Nevertheless, its function in the pathogenesis of periodontitis remains unclear. Here, we investigated the effect of KetoC in a mouse model of periodontitis and explored the underlying mechanism. Methods Thirty-one 8-week-old male C57BL/6N mice were randomly divided into four groups (non-ligation, non-ligation + KetoC, ligation + Porphyromonas gingivalis, and ligation + P. gingivalis + KetoC) (n = 7/8 mice/group) and given a daily oral gavage of KetoC (15 mg/mL) or vehicle for 2 weeks. To induce periodontitis, a 5-0 silk ligature was placed on the maxillary left second molar on day 7, and P. gingivalis W83 (10(9) colony-forming unit [CFU]) was administered orally every 3 days. On day 14, all mice were euthanized. Alveolar bone destruction was determined from the level of the cemento-enamel junction to the alveolar bone crest. Moreover, bone loss level was confirmed from gingival tissue sections stained with hematoxylin and eosin. The presence of P. gingivalis was quantified using real-time polymerase chain reaction. In vitro, the bacteriostatic and bactericidal effects of KetoC were assessed by analyzing its suppressive activity on the proliferation of P. gingivalis and using a live/dead bacterial staining kit, respectively. A double-bond-deficient metabolite (KetoB) was then used to investigate the importance of double-bond structure in the antimicrobial activity of KetoC on P. gingivalis. Results In vivo, KetoC attenuated alveolar bone destruction and suppressed P. gingivalis in the periodontitis group. In vitro, KetoC (but not KetoB) downregulated the proliferation and viability of P. gingivalis in a dose-dependent manner. Conclusions KetoC reduced alveolar bone destruction in a periodontitis model via its antimicrobial function. Therefore, this bioactive metabolite may be valuable in clinical applications to support periodontal therapy.