Gold nanoparticles modulate the crosstalk between macrophages and periodontal ligament cells for periodontitis treatment
Gold nanoparticles modulate the crosstalk between macrophages and periodontal ligament cells for periodontitis treatment
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金纳米颗粒调节巨噬细胞和牙周膜细胞之间的串扰以治疗牙周炎
DOI：
10.1016/j.biomaterials.2019.03.039
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发表时间：
2019-06-01
期刊：
影响因子：
14
通讯作者：
Yan, Fuhua
中科院分区：
文献类型：
--
作者：
Ni, Can;Zhou, Jing;Yan, Fuhua
由于牙周炎患者牙骨质、牙周韧带和牙槽骨的再生能力有限，牙周炎治疗中失去的牙周器官的再生仍然是一个临床挑战。对于牙周组织再生，由于疾病的传染性，在这种情况下调节炎症反应和牙周细胞的分化是至关重要的。本研究发现，45 nm金纳米颗粒（AuNPs）可通过调节炎症和再生细胞因子的产生，调节巨噬细胞的极化，从而影响人牙周韧带细胞（hPDLCs）的分化，表现出明显的抗炎作用，改善牙周炎症微环境。加上AuNPs对hPDLCs的直接作用，在lps激活的炎性巨噬细胞-hPDLCs共培养系统中，AuNPs调节的巨噬细胞与AuNPs刺激的hPDLCs之间的相互作用显著增强了hPDLCs的牙周组织分化能力。通过大鼠开窗和结扎诱导的牙周炎模型，研究了AuNPs在牙周组织再生和牙周炎治疗中的潜在治疗应用。结果发现，45种AuNPs治疗后，牙周缺损的新生牙周附着体、骨和牙骨质明显增加，牙周炎进展中的组织破坏明显减少。本研究表明，45 nm的AuNPs不仅可以直接调节hpdlc，还可以通过调节巨噬细胞表型来调节牙周组织的早期炎症反应，从而形成一个限制炎症细胞因子水平和骨形态发生蛋白-2 （BMP-2）等修复细胞因子水平的微环境，从而促进PDLC分化，促进牙周组织再生，防止牙周炎的进展。
The regeneration of lost periodontal apparatus in periodontitis treatment remains a clinical challenge due to the limited regenerative capacity of cementum, periodontal ligament and alveolar bone in periodontitis condition. For periodontal tissue regeneration, it is essential to regulate the inflammatory response and the subsequent differentiation of periodontal cells under the condition due to the infectious nature of the disease. In this study, it was noted that 45 nm gold nanoparticles (AuNPs) could exhibit significant anti-inflammatory effect and improve the periodontal inflammatory microenvironment via regulating inflammatory and regenerative cytokine production and modulating macrophage polarization, subsequently affect the differentiation of human periodontal ligament cells (hPDLCs). With the addition of direct effects of AuNPs on hPDLCs, the periodontal tissue differentiation capacity of hPDLCs in LPS-activated inflammatory macrophage-hPDLCs coculture system was significantly enhanced by the interaction between AuNPs-conditioned macrophage and AuNPs-stimulated hPDLCs. The potential therapeutic application of AuNPs in periodontal tissue regeneration and periodontitis treatment was investigated using both rat fenestration and ligature-induced periodontitis models. It was found that the treatment of 45 AuNPs showed significantly increased newly-formed periodontal attachment, bone and cementum in periodontal defect and less tissue destruction in the progression of periodontitis. This study demonstrated that 45 nm AuNPs could not only directly modulate hPDLCs, but also regulate the early inflammatory response of periodontal tissues via the regulation of macrophage phenotypes, therefore, generate a microenvironment with constraint inflammatory cytokine levels and reparative cytokines such as bone morphogenetic protein-2 (BMP-2), leading to PDLC differentiation, periodontal tissue regeneration and the prevention of periodontitis progression.