Zhang Wenjing, Jia Linglu, Zhao Bin, Xiong Yixuan, Wang Ya-Nan, Liang Jin, Xu Xin
School of Stomatology, Shandong University, Jinan, Shandong 250012, P.R. China.
School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China.
Int J Mol Med. 2021 Apr;47(4). doi: 10.3892/ijmm.2021.4872. Epub 2021 Feb 4.
Quercetin (Quer) is a typical antioxidant flavonoid from plants that is involved in bone metabolism, as well as in the progression of inflammatory diseases. Elevated levels of tumor necrosis factor‑α (TNF‑α), a typical pro‑inflammatory cytokine, can affect osteogenesis. In the present study, TNF‑α was used to establish an model of periodontitis. The effects of Quer on, as well as its potential role in the osteogenic response of human periodontal ligament stem cells (hPDLSCs) under TNF‑α‑induced inflammatory conditions and the underlying mechanisms were then investigated. Within the appropriate concentration range, Quer did not exhibit any cytotoxicity. More importantly, Quer significantly attenuated the TNF‑α induced the suppression of osteogenesis‑related genes and proteins, alkaline phosphatase (ALP) activity and mineralized matrix in the hPDLSCs. These findings were associated with the fact that Quer inhibited the activation of the NF‑κB signaling pathway, as well as the expression of NLRP3 inflammation‑associated proteins in the inflammatory microenvironment. Moreover, the silencing of NLRP3 by small interfering RNA (siRNA) was found to protect the hPDLSCs against TNF‑α‑induced osteogenic damage, which was in accordance with the effects of Quer. On the whole, the present study demonstrates that Quer reduces the impaired osteogenesis of hPDLSCs under TNF‑α‑induced inflammatory conditions by inhibiting the NF‑κB/NLRP3 inflammasome pathway. Thus, Quer may prove to be a potential remedy against periodontal bone defects.
槲皮素（Quer）是一种源自植物的典型抗氧化类黄酮，参与骨代谢以及炎症性疾病的进展。肿瘤坏死因子-α（TNF-α）是一种典型的促炎细胞因子，其水平升高会影响成骨作用。在本研究中，使用TNF-α建立了牙周炎模型。随后研究了Quer对TNF-α诱导的炎症条件下人牙周膜干细胞（hPDLSCs）成骨反应的影响及其潜在作用和潜在机制。在适当的浓度范围内，Quer未表现出任何细胞毒性。更重要的是，Quer显著减轻了TNF-α诱导的hPDLSCs中成骨相关基因和蛋白质、碱性磷酸酶（ALP）活性和矿化基质的抑制。这些发现与Quer抑制炎症微环境中NF-κB信号通路的激活以及NLRP3炎症相关蛋白的表达这一事实有关。此外，发现小干扰RNA（siRNA）沉默NLRP3可保护hPDLSCs免受TNF-α诱导的成骨损伤，这与Quer的作用一致。总体而言，本研究表明，Quer通过抑制NF-κB/NLRP3炎性小体途径减少了TNF-α诱导的炎症条件下hPDLSCs受损的成骨作用。因此，Quer可能被证明是一种治疗牙周骨缺损的潜在药物。
