The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST KLOS) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBME), School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Department of Periodontology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Biochim Biophys Acta Mol Cell Res. 2021 Jul;1868(8):119042. doi: 10.1016/j.bbamcr.2021.119042. Epub 2021 Apr 24.
Periodontitis is a widespread chronic infectious-inflammatory disease associated with multiple systemic diseases. Visfatin is an adipokine-enzyme that can be locally produced by human periodontal ligament cells (hPDLCs) and human gingival fibroblasts (hGFs). It can upregulate proinflammatory cytokines and matrix metalloproteinases (MMPs) in various types of cells. However, the effects of visfatin on healthy and inflammatory human periodontal cells as well as the underlying molecular mechanisms remain unclear. This study firstly demonstrated visfatin expression was highly elevated in inflamed human gingiva and Pg LPS-treated hPDLCs. Moreover, recombinant visfatin significantly upregulated the expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and prodegradative factors (EMPPRIN, MMP1, MMP3 and MMP13) in hPDLCs. Next, we found the levels of proinflammatory and prodegradative cytokines were significantly increased in visfatin-overexpressing hPDLCs, and decreased in visfatin-silencing inflammatory hGFs (iGFs) when treated with Pg LPS. In the absence of Pg LPS, visfatin silencing failed to affect the expression of these factors in iGFs, and overexpression of visfatin upregulated MMPs but no other factors in hPDLCs. Furthermore, marked NF-κB pathway activation with increased phosphorylation of p65 was observed in visfatin-overexpressing hPDLCs. BAY11-7082, a specific inhibitor of NF-κB, partially reversed the upregulation proinflammatory and prodegradative factors induced by visfatin overexpression. Taken together, this study showed that visfatin critically regulates Pg LPS-induced proinflammatory/prodegradative effects in healthy and inflammatory periodontal cells partially via NF-κB pathway. The findings suggest that visfatin is closely involved in the development of periodontitis, and may serve as a promising novel biomarker and therapeutic target for periodontitis management.
牙周炎是一种广泛存在的慢性感染性炎症性疾病，与多种系统性疾病有关。内脂素是一种脂肪细胞-酶，可由人牙周韧带细胞（hPDLCs）和人牙龈成纤维细胞（hGFs）局部产生。它可以上调各种细胞中的促炎细胞因子和基质金属蛋白酶（MMPs）。然而，内脂素对健康和炎症性人牙周细胞的影响以及潜在的分子机制尚不清楚。本研究首先证明了内脂素在发炎的人牙龈和 Pg LPS 处理的 hPDLCs 中表达水平显著升高。此外，重组内脂素显著上调了 hPDLCs 中促炎细胞因子（TNF-α、IL-1β 和 IL-6）和促降解因子（EMPPRIN、MMP1、MMP3 和 MMP13）的表达。接下来，我们发现在内脂素过表达的 hPDLCs 中，促炎和促降解细胞因子的水平显著增加，而在用 Pg LPS 处理时，内脂素沉默的炎症性 hGFs（iGFs）中这些因子的水平降低。在没有 Pg LPS 的情况下，内脂素沉默未能影响 iGFs 中这些因子的表达，而过表达内脂素上调了 MMPs，但对 hPDLCs 中的其他因子没有影响。此外，还观察到内脂素过表达的 hPDLCs 中 NF-κB 通路的明显激活，p65 的磷酸化增加。NF-κB 的特异性抑制剂 BAY11-7082 部分逆转了内脂素过表达诱导的促炎和促降解因子的上调。总之，本研究表明，内脂素在健康和炎症性牙周细胞中，部分通过 NF-κB 通路，对 Pg LPS 诱导的促炎/促降解作用具有重要的调节作用。研究结果表明，内脂素与牙周炎的发生密切相关，可能成为牙周炎治疗的一个有前途的新型生物标志物和治疗靶点。
