Resolvin E1 accelerates pulp repair by regulating inflammation and stimulating dentin regeneration in dental pulp stem cells.
Resolvin E1 accelerates pulp repair by regulating inflammation and stimulating dentin regeneration in dental pulp stem cells.
复制标题
Resolvin E1 通过调节炎症和刺激牙髓干细胞中的牙本质再生来加速牙髓修复
DOI：
10.1186/s13287-021-02141-y
复制
发表时间：
2021-01-22
影响因子：
7.5
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Chen J;Xu H;Xia K;Cheng S;Zhang Q
背景牙髓炎和组织破坏被认为是牙髓修复失败的原因之一.牙髓干细胞（DPSCs）作为损伤反应的关键介质，在牙髓组织的修复和再生中发挥着重要作用。Resolvin E1（RvE 1）是一种主要的膳食omega-3多不饱和脂肪酸代谢物，可有效缓解炎症和促进伤口愈合。然而，RvE 1是否通过及时解决炎症和DPSC的快速动员来促进受损牙髓组织的修复和再生尚不清楚。因此，我们建立了一个牙髓损伤模型，并研究了影响RvE 1对DPSC介导的炎症决议和损伤的牙髓repair.MethodsA牙髓损伤模型建立8周龄的Sprague-Dawley大鼠。在用浸在含RvE 1的PBS或PBS中的胶原海绵盖髓后第1、3、7、14、21和28天处死动物。苏木精-伊红和Masson三色染色，免疫组织化学和荧光染色用于评估RvE 1的促愈合特性。将hDPSC与脂多糖（LPS）孵育以诱导炎症反应，并测量RvE 1应用后炎症因子的表达。采用CCK-8法、transwell法、碱性磷酸酶（ALP）染色、茜素红染色、定量PCR等方法研究RvE 1对hDPSC增殖、趋化性和牙向分化的影响，并采用westernblotting.ResultsIn体内，RvE 1可降低损伤牙髓坏死率，保存更多活髓，促进损伤牙髓修复和修复性牙本质形成。此外，它还增强牙本质基质蛋白1和牙本质唾液蛋白的表达，并通过抑制TNF-α和IL-1β的表达来加速牙髓炎症的消退。RvE 1促进CD 146+和CD 105 +DPSCs向受损磨牙牙髓间充质的募集。分离的原代细胞表现出间充质干细胞的免疫表型和分化。RvE 1促进hDPSC增殖和趋化。RvE 1可显著抑制LPS刺激的DPSCs中促炎细胞因子（TNF-α、IL-1β和IL-6）的释放，并增强ALP活性、结节矿化，尤其是牙形成相关基因DMP 1、DSPP和BSP的表达。结论RvE 1可促进牙髓炎症反应的缓解和牙本质再生，并对LPS刺激的hDPSCs的增殖、趋化和分化有积极影响。这种反应至少部分依赖于炎症微环境中的AKT、ERK和rS6相关信号传导。RvE 1在再生牙髓病学中具有良好的应用前景。
BackgroundUnresolved inflammation and tissue destruction are considered to underlie the failure of dental pulp repair. As key mediators of the injury response, dental pulp stem cells (DPSCs) play a critical role in pulp tissue repair and regeneration. Resolvin E1 (RvE1), a major dietary omega-3 polyunsaturated fatty-acid metabolite, is effective in resolving inflammation and activating wound healing. However, whether RvE1 facilitates injured pulp-tissue repair and regeneration through timely resolution of inflammation and rapid mobilization of DPSCs is unknown. Therefore, we established a pulp injury model and investigated the effects of RvE1 on DPSC-mediated inflammation resolution and injured pulp repair.MethodsA pulp injury model was established using 8-week-old Sprague-Dawley rats. Animals were sacrificed on days 1, 3, 7, 14, 21, and 28 after pulp capping with a collagen sponge immersed in PBS with RvE1 or PBS. Hematoxylin-eosin and Masson’s trichrome staining, immunohistochemistry, and immunohistofluorescence were used to evaluate the prohealing properties of RvE1. hDPSCs were incubated with lipopolysaccharide (LPS) to induce an inflammatory response, and the expression of inflammatory factors after RvE1 application was measured. Effects of RvE1 on hDPSC proliferation, chemotaxis, and odontogenic differentiation were evaluated by CCK-8 assay, transwell assay, alkaline phosphatase (ALP) staining, alizarin red staining, and quantitative PCR, and possible signaling pathways were explored using western blotting.ResultsIn vivo, RvE1 reduced the necrosis rate of damaged pulp and preserved more vital pulps, and promoted injured pulp repair and reparative dentin formation. Further, it enhanced dentin matrix protein 1 and dentin sialoprotein expression and accelerated pulp inflammation resolution by suppressing TNF-α and IL-1β expression. RvE1 enhanced the recruitment of CD146+and CD105+DPSCs to the damaged molar pulp mesenchyme. Isolated primary cells exhibited the mesenchymal stem cell immunophenotype and differentiation. RvE1 promoted hDPSC proliferation and chemotaxis. RvE1 significantly attenuated pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) release and enhanced ALP activity, nodule mineralization, and especially, expression of the odontogenesis-related genesDMP1,DSPP, andBSPin LPS-stimulated DPSCs. RvE1 regulated AKT, ERK, and rS6 phosphorylation in LPS-stimulated DPSCs.ConclusionsRvE1 promotes pulp inflammation resolution and dentin regeneration and positively influences the proliferation, chemotaxis, and differentiation of LPS-stimulated hDPSCs. This response is, at least partially, dependent on AKT, ERK, and rS6-associated signaling in the inflammatory microenvironment. RvE1 has promising application potential in regenerative endodontics.
登录
查看更多内容
影响因子：
0.7
作者：
Lovschall, Henrik;Mitsiadis, Thimios A.;Kjeldsen, Annette L.
通讯作者：
Kjeldsen, Annette L.
基于纳米纤维膜核壳胶束定时药物释放的牙周炎一步治疗
影响因子：
10.8
作者：
Liu, Xiaochen;Zhang, Wenxin;Huang, Chen
通讯作者：
Huang, Chen
影响因子：
4.4
作者：
Hasturk, Hatice;Kantarci, Alpdogan;Van Dyke, Thomas E.
通讯作者：
Van Dyke, Thomas E.
影响因子：
4.2
作者：
Colombo JS;Moore AN;Hartgerink JD;D'Souza RN
通讯作者：
D'Souza RN
影响因子：
4.6
作者：
Gaudin A;Tolar M;Peters OA
通讯作者：
Peters OA