Song Aishi, Wang Wei, Zhang Yuying, Zhou Peng, Li Jiaxing, Habimana Jean de Dieu, Mukama Omar, Xie Wei, Deng Sihao, Zhang Shusheng, Li Ming, Ni Bin, Tang Yabing, Yan Xiao-Xin, Huang Jufang, Li Zhiyuan
Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha 410013, China.
CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663, China.
J Tissue Eng Regen Med. 2023 Nov 3;2023:3077814. doi: 10.1155/2023/3077814. eCollection 2023.
Periodontitis is characterized by bone resorption and periodontal tissue destruction owing to oral microbiota, mechanical stress, and systemic diseases such as diabetes mellitus. Human dental pulp mesenchymal stem cells (hDPMSCs) were analyzed as potential candidates for periodontal tissue regeneration. Acetylsalicylic acid (ASA), also known as aspirin, has been shown to promote osteogenic differentiation of mesenchymal stem cells. We investigated the effect of ASA pretreatment on periodontitis in order to achieve a more appealing prognosis of bone resorption.
The effect of ASA on cell proliferation was detected by the CCK-8 assay, and alkaline phosphatase (ALP) staining, alizarin red staining (ARS), and western blot were used to investigate the effect of different ASA concentrations on hDPMSCs' osteogenic differentiation and possible signaling pathways. Periodontitis was induced for 4 weeks. Stem cells pretreated with 50 g/mL of ASA were transplanted into six-week-old male Sprague-Dawley rats by local and systemic injection once a week for two weeks. Four weeks after cell therapy, the rats were sacrificed for sampling to complete the molecular and morphological experiments.
In vitro experiments revealed that 50 g/mL of ASA had a significant effect on cell osteogenic differentiation. That is, when ASA was administered, the MAPK signaling pathway was activated. Notably, further vivo experiments revealed that ASA-hDPMSCs increased the area of bone regeneration and the OPG/RANKL ratio, suppressed TNF- and IL-1 expression, and promote alveolar bone repair.
Our study extends the findings of previous research, firstly demonstrating that the use of ASA-pretreated hDPMSCs offers a novel therapy for the treatment of periodontitis for future clinical application.
牙周炎的特征是由于口腔微生物群、机械应力以及糖尿病等全身性疾病导致骨吸收和牙周组织破坏。人牙髓间充质干细胞（hDPMSCs）被分析作为牙周组织再生的潜在候选细胞。乙酰水杨酸（ASA），也被称为阿司匹林，已被证明可促进间充质干细胞的成骨分化。我们研究了ASA预处理对牙周炎的影响，以实现更理想的骨吸收预后。
通过CCK-8法检测ASA对细胞增殖的影响，并用碱性磷酸酶（ALP）染色、茜素红染色（ARS）和蛋白质印迹法研究不同浓度ASA对hDPMSCs成骨分化及可能的信号通路的影响。诱导牙周炎4周。将用50μg/mL ASA预处理的干细胞通过局部和全身注射，每周一次，共两周，移植到六周龄雄性Sprague-Dawley大鼠体内。细胞治疗四周后，处死大鼠取样以完成分子和形态学实验。
体外实验表明，50μg/mL ASA对细胞成骨分化有显著影响。也就是说，当给予ASA时，MAPK信号通路被激活。值得注意的是，进一步的体内实验表明，ASA-hDPMSCs增加了骨再生面积和OPG/RANKL比值，抑制了TNF-和IL-1的表达，并促进了牙槽骨修复。
我们的研究扩展了先前研究的结果，首次证明使用ASA预处理的hDPMSCs为未来临床治疗牙周炎提供了一种新的治疗方法。
