CCR3 antagonist protects against induced cellular senescence and promotes rejuvenation in periodontal ligament cells for stimulating pulp regeneration in the aged dog
CCR3 antagonist protects against induced cellular senescence and promotes rejuvenation in periodontal ligament cells for stimulating pulp regeneration in the aged dog
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DOI：
10.1038/s41598-020-65301-9
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发表时间：
2020-05
影响因子：
4.6
通讯作者：
Mohammed Zayed;K. Iohara;H. Watanabe;M. Nakashima
中科院分区：
文献类型：
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作者：
Mohammed Zayed;K. Iohara;H. Watanabe;M. Nakashima
老年犬移植动员牙髓干细胞(MDPSCs)后牙髓再生能力下降，部分原因是慢性炎症和/或细胞衰老。嗜酸性粒细胞趋化因子-1/C-C基序趋化因子11(CCL11)是通过趋化因子受体3(CCR3)表达的炎症标志物。此外，CCR3拮抗剂(CCR3A)可抑制CCL11与CCR3的结合，阻止CCL11/CCR3信号转导。本研究旨在探讨CCR3A对人牙周膜细胞(HPDLCs)细胞衰老和抗炎/免疫调节的影响。在体内，与未加CCR3A的对照相比，移植CCR3A的MDPSCs再生牙髓组织的数量显著增加。体外，经对甲酚暴露后，HPDLCs被诱导衰老，表现为细胞体积增大，增殖减少，衰老标记物p21和IL-1β增加。CCR3A处理HPDLCs可阻止对甲酚的衰老作用。此外，CCR3A显著降低CCL11的表达，增加免疫调节因子IDO的表达，增强轴突的延伸和迁移活性。综上所述，CCR3A可防止对甲酚诱导的细胞衰老，增强年轻效应，提示其在促进老年牙齿牙髓再生方面具有潜在的应用价值。
Pulp regeneration after transplantation of mobilized dental pulp stem cells (MDPSCs) declines in the aged dogs due in part to the chronic inflammation and/or cellular senescence. Eotaxin-1/C-C motif chemokine 11 (CCL11) is an inflammation marker via chemokine receptor 3 (CCR3). Moreover, CCR3 antagonist (CCR3A) can inhibit CCL11 binding to CCR3 and prevent CCL11/CCR3 signaling. The study aimed to examine the effect of CCR3A on cellular senescence and anti-inflammation/immunomodulation in human periodontal ligament cells (HPDLCs). The rejuvenating effects of CCR3A on neurite extension and migratory activity to promote pulp regeneration in aged dog teeth were also evaluated.In vivo, the amount of regenerated pulp tissues was significantly increased by transplantation of MDPSCs with CCR3A compared to control without CCR3A.In vitro, senescence of HPDLCs was induced afterp-Cresol exposure, as indicated by increased cell size, decreased proliferation and increased senescence markers,p21andIL-1β. Treatment of HPDLCs with CCR3A prevented the senescence effect ofp-Cresol. Furthermore, CCR3A significantly decreased expression of CCL11, increased expression of immunomodulatory factor, IDO, and enhanced neurite extension and migratory activity. In conclusion, CCR3A protects againstp-Cresol-induced cellular senescence and enhances rejuvenating effects, suggesting its potential utility to stimulate pulp regeneration in the aged teeth.