The use of TLR2 modified BMSCs for enhanced bone regeneration in the inflammatory micro-environment

The use of TLR2 modified BMSCs for enhanced bone regeneration in the inflammatory micro-environment
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使用 TLR2 修饰的 BMSC 增强炎症微环境中的骨再生

DOI:
10.1080/21691401.2019.1626867
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发表时间:
2019-08
影响因子:
5.8
通讯作者:
Zheng Jiawei
Zheng Jiawei
中科院分区:
工程技术2区
文献类型:
--
作者:
Zhou Qin;Gu Xiaoyu;Dong Jiachen;Zhu Chao;Cai Zhen;He Dongmei;Yang Chi;Xu Ling;Zheng Jiawei

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摘要牙周炎患者牙周骨组织缺损的修复是口腔医师面临的主要挑战之一。基于干细胞的骨再生被认为是修复牙周骨组织缺损的一种有前途的策略。然而,牙周组织的局部炎症环境影响了基于干细胞的牙周骨再生。Toll样受体2(TLR 2)是TLR家族的成员之一,在免疫反应中起着重要的调节作用。以往的研究表明,TLR 2信号通路的激活参与促进组织血管化和伤口愈合。然而,TLR 2调控骨髓基质细胞(BMSCs)介导的牙周骨组织再生的治疗作用的机制仍需进一步研究。在本研究中,我们通过使用慢病毒建立TLR 2基因修饰的犬BMSCs来检测TLR 2对BMSCs介导的牙槽骨再生的调节作用。TLR 2的激活可显著增强BMSCs中缺氧诱导因子-1 α(HIF-1α)和骨形态发生蛋白-2(BMP-2)的表达,进而上调其下游成骨和血管生成相关基因的表达。TLR 2-BMSCs介导的炎症环境下犬拔牙窝中的骨再生表明,TLR 2信号通路的激活显着刺激BMSCs介导的血管生成和成骨。
Abstract The repair of periodontal bone tissue defects in patients with periodontitis is one of the major challenges for dentists. Stem cell-based bone regeneration has been considered as a promising strategy to restore the lost periodontal bone tissue. However, the local inflammatory environment of periodontal tissue affects stem cell-based periodontal bone regeneration. Toll-like receptor 2 (TLR2), a member of the TLR family, plays an important role in regulating immunoreaction. Previous studies have shown that the activation of TLR2 signaling pathway is involved in enhancing tissue vascularization and wound healing. However, the mechanisms underlying the therapeutic effects of TLR2 on regulating bone marrow stromal cells (BMSCs) mediated periodontal bone tissue regeneration still need to be further investigated. In this study, we tested the effect of TLR2 on regulating BMSCs mediated alveolar bone regeneration by establishing a TLR2 gene-modified canine BMSCs using a lentivirus. Activation of TLR2 significantly enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and bone morphogenetic protein 2 (BMP-2) and then upregulated the expression of their downstream osteogenic and angiogenic related gene in BMSCs. TLR2-BMSCs mediated bone regeneration in canine tooth extraction sockets under an inflammatory environment demonstrated that activation of the TLR2 signaling pathway significantly stimulated BMSCs meditated angiogenesis and osteogenesis.
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发表时间: 2009-06
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