Periodontal disease is a significant public health problem worldwide. Excess unresolved chronic inflammation destroys the periodontal tissues that surround and support the teeth, and efforts to control inflammation by removal of bacterial deposits on the teeth have limited long-term impact. Likewise, procedures aimed at regeneration of the periodontal tissues have shown limited success. Recent advances in stem cell research have shown promising novel prospects for the use of periodontal ligament stem cells (PDLSCs) in tissue regeneration; however, control of inflammation remains a barrier. Human PDLSCs have been shown to release specialized proresolving lipid mediators (SPMs) that modulate the immune response and promote resolution of inflammation, tissue repair, and regeneration. Studies on stem cell biology in periodontology have also been limited by the lack of a good large animal model. Herein, we describe PDLSC biology of the Yorkshire pig (pPDLSCs). pPDLSCs were isolated and characterized. Using lipid mediator profiling, we demonstrate for the first time that pPDLSCs biosynthesize cysteinyl-containing SPMs (cys-SPMs), specifically, maresin conjugates in tissue regeneration 3 (MCTR3) and its authentication using liquid chromatography/tandem mass spectrometry. The exogenous addition of the n-3 precursor docosahexaenoic acid enhances MCTR3 biosynthesis. Using immunocytochemistry, we show that pPDLSCs express 4 of the SPM biosynthetic pathway enzymes necessary for SPM biosynthesis, including 5-lipoxygenase, 12-lipoxygenase, and 15-lipoxygenase-1. In addition, we identified and quantified the cytokine/chemokine profile of pPDLSCs using a 13-plex immunology multiplex assay and found that the pretreatment of pPDLSCs with MCTR3 in an inflammatory environment reduced the production of acute and chronic proinflammatory cytokines/chemokines. Together, these results suggest that enhancing resolution of inflammation pathways and mediators may be a possible key early event in predictable periodontal regeneration.

牙周病是世界范围内重要的公共卫生问题。过多的未解决的慢性炎症会破坏包围和支撑牙齿的牙周组织，通过清除牙齿上的细菌沉积物来控制炎症的长期影响有限。同样，旨在牙周组织再生的手术也取得了有限的成功。干细胞研究的最新进展表明，牙周膜干细胞（PDLSC）在组织再生中的应用具有广阔的前景。然而，炎症的控制仍然是一个障碍。人类 PDLSC 已被证明可以释放专门的促消解脂质介质 (SPM)，调节免疫反应并促进炎症消退、组织修复和再生。牙周病学中干细胞生物学的研究也因缺乏良好的大型动物模型而受到限制。在此，我们描述了约克夏猪 (pPDLSC) 的 PDLSC 生物学。 pPDLSC 被分离并表征。使用脂质介质分析，我们首次证明 pPDLSC 生物合成含有半胱氨酰基的 SPM (cys-SPM)，特别是组织再生中的 maresin 缀合物 3 (MCTR3)，并使用液相色谱/串联质谱法对其进行验证。外源添加 n-3 前体二十二碳六烯酸可增强 MCTR3 生物合成。使用免疫细胞化学，我们表明 pPDLSC 表达 SPM 生物合成所需的 4 种 SPM 生物合成途径酶，包括 5-脂氧合酶、12-脂氧合酶和 15-脂氧合酶-1。 此外，我们使用 13 重免疫学多重测定对 pPDLSC 的细胞因子/趋化因子谱进行了鉴定和定量，发现在炎症环境中用 MCTR3 预处理 pPDLSC 减少了急性和慢性促炎细胞因子/趋化因子的产生。总之，这些结果表明，增强炎症途径和介质的分辨率可能是可预测的牙周再生的一个可能的关键早期事件。