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-炎症性疾病，与多种全身性疾病相关。内脂素是一种脂肪因子酶，可由人牙周膜细胞 (hPDLC) 和人牙龈成纤维细胞 (hGF) 局部产生。它可以上调各种类型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人类牙周细胞的影响以及潜在的分子机制仍不清楚。这项研究首先证明了发炎的人牙龈和Pg 中内脂素的​​表达高度升高LPS 处理的 hPDLC。此外，重组内脂素显着上调 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，我们发现当用Pg LPS处理时，内脂素过表达的 hPDLC 中促炎和促降解细胞因子的水平显着增加，而内脂素沉默的炎性 hGF (iGF) 中的促炎和促降解细胞因子水平降低。在没有Pg的情况下LPS、内脂素沉默未能影响这些因子在 iGF 中的表达，内脂素的过表达上调了 MM​​P，但没有影响 hPDLC 中的其他因子。此外，在过表达内脂素的 hPDLC 中观察到显着的 NF-κB 通路激活和 p65 的磷酸化增加。BAY11-7082 是一种 NF-κB 的特异性抑制剂，可部分逆转由内脂素过表达诱导的促炎和促降解因子的上调。综上所述，这项研究表明内脂素对PgLPS 在健康和炎症牙周细胞中部分通过 NF-κB 途径诱导的促炎/促降解作用。研究结果表明，visfatin 与牙周炎的发展密切相关，可能作为牙周炎管理的一种有前途的新型生物标志物和治疗靶点。