State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Cell Death Dis. 2019 Jan 8;10(1):20. doi: 10.1038/s41419-018-1253-y.
Accumulating evidence indicates that the pluripotency of periodontal ligament stem cells (PDLSCs) is compromised under inflammatory conditions; however, the underlying mechanisms remain largely unexplored. In this study, we hypothesize that the P2X7 receptor (P2X7R) is a key molecule linked to inflammation-associated impairment of PDLSCs. We first investigated P2X7R expression in PDLSCs under normal and inflammatory conditions and then determined the effect of a P2X7R agonist (BzATP) or antagonist (BBG) on PDLSC osteogenesis under various conditions. Gene-modified PDLSCs were used to further examine the role of P2X7R and the signaling pathway underlying P2X7R-enhanced osteogenesis. We found that inflammatory conditions decreased P2X7R expression in PDLSCs and reduced osteogenesis in these cells. In addition, activation of P2X7R by BzATP or overexpression of P2X7R via gene transduction reversed the inflammation-mediated decrease in PDLSC osteogenic differentiation. When selected osteogenesis-related signaling molecules were screened, the PI3K-AKT-mTOR pathway was identified as potentially involved in P2X7R-enhanced PDLSC osteogenesis. Our data reveal a crucial role for P2X7R in PDLSC osteogenesis under inflammatory conditions, suggesting a new therapeutic target to reverse or rescue inflammation-mediated changes in PDLSCs for future mainstream therapeutic uses.
越来越多的证据表明，牙周膜干细胞（PDLSCs）的多能性在炎症条件下受到损害；然而，其潜在机制在很大程度上仍未得到探索。在本研究中，我们假设 P2X7 受体（P2X7R）是与炎症相关的 PDLSCs 损伤相关的关键分子。我们首先研究了正常和炎症条件下 PDLSCs 中 P2X7R 的表达，然后确定了 P2X7R 激动剂（BzATP）或拮抗剂（BBG）在各种条件下对 PDLSC 成骨的影响。基因修饰的 PDLSCs 用于进一步研究 P2X7R 的作用以及 P2X7R 增强成骨作用的信号通路。我们发现炎症条件降低了 PDLSCs 中 P2X7R 的表达，并减少了这些细胞的成骨作用。此外，BzATP 激活 P2X7R 或通过基因转导过表达 P2X7R 逆转了炎症介导的 PDLSC 成骨分化减少。当筛选出与成骨相关的信号分子时，发现 PI3K-AKT-mTOR 通路可能参与了 P2X7R 增强 PDLSC 成骨作用。我们的数据揭示了 P2X7R 在炎症条件下 PDLSC 成骨中的关键作用，为未来主流治疗用途中逆转或挽救 PDLSCs 炎症介导的变化提供了一个新的治疗靶点。
