引言
牙结石可引起牙龈出血和牙周炎,但形成这种矿物质积聚的机制,特别是局部微环境的作用,尚不清楚。
2024年3月15日,空军军医大学牛丽娜团队在
Nature Biomedical Engineering
在线发表题为“
Bacteria-mediated resistance of neutrophil extracellular traps to enzymatic degradation drives the formation of dental calculi
”的研究论文,
该研究发现结石的形成涉及局部成熟生物膜中的细菌将中性粒细胞胞外陷阱(
NETs
)中的DNA从可被DNase I酶降解转化为抗降解,促进磷灰石的成核和生长。
DNase I在体外和离体均能抑制NET诱导的矿化,但血浆DNase对啮齿动物口腔内异位矿化无效。局部应用DNA插入剂氯喹在啮齿动物喂养的牙结石饮食恢复NET DNA的可降解形式,抑制结石的形成。该研究可能会激发治疗策略,以减少细菌驱动的结石在口腔沉积的患病率。
超过一半的人患有牙石,它会导致牙周炎、牙齿脱落甚至心血管疾病。
即使由经验丰富的牙医取出结石后,结石的复发率仍然很高。了解异位矿化驱动牙结石的机制有助于促进慢性牙周炎的愈合。
然而,目前还没有普遍接受的机制,为临床可行的预防牙结石发生策略的发展提供了基础。
人们假设了不同的机制来解释它们的发展。
这些机制包括牙菌斑矿化、唾液钙含量增加和富含碳水化合物的饮食。虽然这些机制解释了发生在牙石发育中的病理变化,但它们没有考虑宿主免疫反应的贡献。最近的研究报道了胆结石和唾液结石中存在中性粒细胞胞外陷阱(NETs) 。
虽然口腔内的牙结石不等同于人体其他部位的矿化堆积,但可以合理地假设先天免疫也参与了牙结石的形成。
模式图(Credit:
Nature Biomedical Engineering)
该研究提出NETs与牙结石的矿化有关。
为了验证这一假设,研究人员最初开发了一种类似于体外显微镜
异位钙化
的NET -生物矿物复合物。在这个复合体中,NET脱氧核糖核酸(NET DNA)通过启动矿物形成参与了牙石的发育。偶然发现,除了NETs之外,生物膜细菌还需要通过将NETs转化为不能被酶降解的耐DNA-I手性形式来协调牙石的形成。抑制细菌改变的NETs在体内和体外均能有效防止牙结石的形成。
该研究为预防细菌驱动的牙结石异位矿化提供了概念基础。
|探索君
排版|探索君
文章来源|“iNature”
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