MicroRNA-enriched small extracellular vesicles possess odonto-immunomodulatory properties for modulating the immune response of macrophages and promoting odontogenesis.
MicroRNA-enriched small extracellular vesicles possess odonto-immunomodulatory properties for modulating the immune response of macrophages and promoting odontogenesis.
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富含MicroRNA的小细胞外囊泡具有成牙免疫调节特性，可调节巨噬细胞的免疫反应并促进成牙
DOI：
10.1186/s13287-020-02039-1
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发表时间：
2020-11-30
影响因子：
7.5
通讯作者：
Ling J
中科院分区：
文献类型：
--
作者：
Zheng J;Kong Y;Hu X;Li Z;Li Y;Zhong Y;Wei X;Ling J
研究牙髓干细胞衍生的小细胞外囊泡（DPSCs-sEV）通过将巨噬细胞转换为促愈合的M2表型来促进牙髓形成的牙免疫调节特性。对DPSCs-sEV进行MicroRNA测序，进行MicroRNA谱分析。通过自动Western blot、qPCR、ELISA和流式细胞术鉴定巨噬细胞中富集microrna的DPSCs-sEV的功能。荧光素酶报告基因检测证实外泌体miR-125a-3p的直接靶基因。利用DPSCs- sev刺激的巨噬细胞条件培养基促进DPSCs成牙，探讨DPSCs- sev刺激下成牙的免疫应答机制。将DPSCs-sEV注射到暴露的大鼠切牙牙髓组织中，研究DPSCs-sEV在体内对牙体免疫的调节作用。DPSCs-sEV通过抑制TLR和NFκΒ信号通路将巨噬细胞转变为促愈合的M2表型。MicroRNA测序发现，81个MicroRNA在DPSCS-sEV中显著改变，其中miR-125a-3p表达上调12倍。外泌体miR-125a-3p通过直接靶向IKBKB抑制NFκΒ和TLR信号传导，将巨噬细胞转变为M2表型。有趣的是，DPSCs- sev和被封装的miR-125a-3p增强巨噬细胞中BMP2的释放，通过BMP2通路激活促进DPSCs的牙生成。大鼠研究证实，DPSCs-sEV可以作为理想的仿生工具，通过将巨噬细胞转变为促愈合的M2细胞来促进牙生成。我们首先定义了microrna富集的DPSCs-sEV的牙齿免疫调节特性，它可以作为理想的仿生工具，通过将巨噬细胞转向促愈合的M2表型来促进牙齿形成。
To investigate the odonto-immunomodulatory properties of dental pulp stem cell-derived small extracellular vesicles (DPSCs-sEV), which promote odontogenesis by switching macrophages toward the pro-healing M2 phenotype. MicroRNA sequencing was carried out for microRNA profiling of DPSCs-sEV. Automated Western blot, qPCR, ELISA, and flow cytometry were performed to identify the functions of microRNA-enriched DPSCs-sEV in macrophages. A luciferase reporter gene assay was carried out to confirm exosomal miR-125a-3p’s direct target gene. DPSCs-sEV-stimulated macrophage-conditioned media were used to promote odontogenesis in DPSCs and explore the mechanism of immune response in DPSCs-SEV-stimulated odontogenesis. DPSCs-sEV were injected into the exposed pulp tissue of rat incisor to investigate the odonto-immunomodulatory properties of DPSCs-sEV in vivo. DPSCs-sEV switched macrophages to the pro-healing M2 phenotype by inhibiting TLR and NFκΒ signaling. MicroRNA sequencing found 81 microRNAs significantly altered in DPSCS-sEV, with miR-125a-3p showing a 12-fold upregulation. Exosomal miR-125a-3p switched macrophages toward the M2 phenotype via inhibiting NFκΒ and TLR signaling via direct IKBKB targeting. Interestingly, DPSCs-sEV and the encapsulated miR-125a-3p enhanced BMP2 release in macrophages, promoting odontogenesis in DPSCs through BMP2 pathway activation. The rat study confirmed that DPSCs-sEV could be used as ideal biomimetic tools to enhance odontogenesis by switching macrophages toward pro-healing M2 cells. We firstly defined the odonto-immunomodulatory properties of microRNA-enriched DPSCs-sEV, which could be used as ideal biomimetic tools to enhance odontogenesis by switching macrophages toward the pro-healing M2 phenotype.
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DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
β-磷酸三钙通过 BMP2 信号通路刺激巨噬细胞诱导骨髓 MSC 成骨分化
影响因子：
14
作者：
Chen, Zetao;Wu, Chengtie;Xiao, Yin
通讯作者：
Xiao, Yin
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：
3.3
作者：
Moussa DG;Aparicio C
通讯作者：
Aparicio C
影响因子：
14
作者：
Brown, Bryan N.;Valentin, Jolene E.;Stewart-Akers, Ann M.;McCabe, George P.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.