a Department of Oral and Maxillofacial Surgery, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai , China.
b Department of Prothodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3329-3337. doi: 10.1080/21691401.2019.1626867.
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.
牙周炎患者的牙周骨组织缺损修复是口腔医生面临的主要挑战之一。基于干细胞的骨再生被认为是恢复牙周失骨组织的一种很有前途的策略。然而，牙周组织的局部炎症环境影响基于干细胞的牙周骨再生。Toll 样受体 2（TLR2）是 TLR 家族的成员，在调节免疫反应中发挥重要作用。先前的研究表明，TLR2 信号通路的激活参与增强组织血管生成和伤口愈合。然而，TLR2 调节骨髓基质细胞（BMSCs）介导的牙周骨组织再生的治疗作用的机制仍需要进一步研究。在这项研究中，我们通过使用慢病毒建立 TLR2 基因修饰的犬 BMSCs，测试了 TLR2 对调节 BMSCs 介导的牙槽骨再生的影响。TLR2 的激活显著增强了低氧诱导因子 1α（HIF-1α）和骨形态发生蛋白 2（BMP-2）的表达，随后上调了 BMSCs 中其下游成骨和成血管相关基因的表达。在炎症环境下，犬牙拔除窝中 TLR2-BMSCs 介导的骨再生表明，TLR2 信号通路的激活显著刺激了 BMSCs 介导的血管生成和成骨作用。
