Department of Implantology, Stomatological Hospital of Xiamen Medical College, Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment, Xiamen 361008, China.
Dongfeng Stomatological Hospital, Hubei University of Medicine, Shiyan 442000, China.
Prostaglandins Other Lipid Mediat. 2024 Oct;174:106882. doi: 10.1016/j.prostaglandins.2024.106882. Epub 2024 Aug 14.
Periodontitis is featured as the periodontium's pathologic destruction caused by the host's overwhelmed inflammation. Omentin-1 has been reported to be aberrantly downregulated in patients with periodontitis, but the specific regulation of Omentin-1 during the pathogenesis of periodontitis remains unclear. In this study, human periodontal ligament stem cells (hPDLSCs) were stimulated by lipopolysaccharide (LPS) from Porphyromonas gingivalis to establish an in vitro inflammatory periodontitis model. hPDLSCs were treated with recombinant human Omentin-1 (250, 500 and 750 ng/mL) for 3 h before LPS stimulation. Results revealed that Omentin-1 significantly inhibited LPS-induced inflammation in hPDLSCs through reducing the production of proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6) and downregulating the expression of Cox2 and iNOS. Meanwhile, Omentin-1 significantly enhanced alkaline phosphatase (ALP) activity and Alizarin red-stained area, accompanied by increasing expression osteogenic markers BMP2, OCN and Runx2, confirming that Omentin-1 restores osteogenic differentiation in LPS-induced hPDLSCs. In addition, the conditioned medium (CM) from LPS-induced hPDLSCs was harvested to culture macrophages, which resulted in macrophage polarization towards M1, while CM from Omentin-1-treated hPDLSCs reduced M1 macrophages polarization and elevated M2 polarization. Furthermore, Omentin-1 also inhibited LPS-triggered endoplasmic reticulum (ER) stress in hPDLSCs, and additional treatment of the ER stress activator tunicamycin (TM) partially reversed the functions of Omentin-1 on inflammation, osteogenic differentiation and macrophages polarization. In summary, Omentin-1 exerted a protective role against periodontitis through inhibiting inflammation and enhancing osteogenic differentiation of hPDLSCs, providing a novelty treatment option for periodontitis.
牙周炎是以宿主过度炎症反应为特征的牙周组织病理性破坏。已有研究报道，网膜素-1在牙周炎患者中异常下调，但网膜素-1在牙周炎发病机制中的具体调控作用尚不清楚。本研究采用牙龈卟啉单胞菌脂多糖（LPS）刺激人牙周膜干细胞（hPDLSCs）建立体外炎症性牙周炎模型。在 LPS 刺激前，用重组人网膜素-1（250、500 和 750ng/mL）处理 hPDLSCs 3h。结果表明，网膜素-1通过减少促炎细胞因子（肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β和 IL-6）的产生和下调 Cox2 和 iNOS 的表达，显著抑制 LPS 诱导的 hPDLSCs 炎症反应。同时，网膜素-1显著增强碱性磷酸酶（ALP）活性和茜素红染色面积，伴随着骨形成标志物 BMP2、OCN 和 Runx2 的表达增加，证实网膜素-1恢复了 LPS 诱导的 hPDLSCs 成骨分化。此外，从 LPS 诱导的 hPDLSCs 中收集条件培养基（CM）培养巨噬细胞，导致巨噬细胞向 M1 极化，而用网膜素-1处理的 hPDLSCs 的 CM 减少了 M1 巨噬细胞极化并增加了 M2 极化。此外，网膜素-1还抑制了 LPS 触发的 hPDLSCs 内质网（ER）应激，并用 ER 应激激活剂衣霉素（TM）进行额外处理部分逆转了网膜素-1对炎症、成骨分化和巨噬细胞极化的作用。总之，网膜素-1通过抑制炎症和增强 hPDLSCs 的成骨分化发挥对牙周炎的保护作用，为牙周炎提供了一种新的治疗选择。
