Department of Oral Biology, University of Illinois Chicago, Chicago, IL, USA.
Connect Tissue Res. 2023 Sep;64(5):505-515. doi: 10.1080/03008207.2023.2218944. Epub 2023 May 29.
Inflammation is a complex host response to harmful infection or injury, and it seems to play a crucial role in tissue regeneration both positively and negatively. We have previously demonstrated that the activation of the complement C5a pathway affects dentin-pulp regeneration. However, limited information is available to understand the role of the complement C5a system related to inflammation-mediated dentinogenesis. The aim of this study was to determine the role of complement C5a receptor (C5aR) in regulating lipopolysaccharide (LPS)-induced odontogenic differentiation of dental pulp stem cells (DPSCs).
Human DPSCs were subjected to LPS-stimulated odontogenic differentiation in dentinogenic media treated with the C5aR agonist and antagonist. A putative downstream pathway of the C5aR was examined using a p38 mitogen-activated protein kinase (p38) inhibitor (SB203580).
Our data demonstrated that inflammation induced by the LPS treatment potentiated DPSC odontogenic differentiation and that this is C5aR dependent. C5aR signaling controlled the LPS-stimulated dentinogenesis by regulating the expression of odontogenic lineage markers like dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP-1). Moreover, the LPS treatment increased the total p38, and the active form of p38 expression, and treatment with SB203580 abolished the LPS-induced DSPP and DMP-1 increase.
These data suggest a significant role of C5aR and its putative downstream molecule p38 in the LPS-induced odontogenic DPSCs differentiation. This study highlights the regulatory pathway of complement C5aR/p38 and a possible therapeutic approach for improving the efficiency of dentin regeneration during inflammation.
炎症是宿主对有害感染或损伤的一种复杂反应，它似乎在组织再生中发挥着积极和消极的关键作用。我们之前的研究表明，补体 C5a 途径的激活会影响牙本质-牙髓的再生。然而，目前对于补体 C5a 系统在炎症介导的牙本质形成中的作用的了解有限。本研究旨在确定补体 C5a 受体（C5aR）在调节脂多糖（LPS）诱导的牙髓干细胞（DPSCs）成牙分化中的作用。
将人 DPSCs 置于牙本质形成培养基中，用 C5aR 激动剂和拮抗剂处理 LPS 刺激的成牙分化。使用 p38 丝裂原活化蛋白激酶（p38）抑制剂（SB203580）检测 C5aR 的下游途径。
我们的数据表明，LPS 处理引起的炎症增强了 DPSC 的成牙分化，这是 C5aR 依赖性的。C5aR 信号通过调节牙本质涎磷蛋白（DSPP）和牙本质基质蛋白 1（DMP-1）等牙原性标志物的表达来控制 LPS 刺激的牙本质形成。此外，LPS 处理增加了总 p38 和活性形式的 p38 的表达，而 SB203580 的处理消除了 LPS 诱导的 DSPP 和 DMP-1 的增加。
这些数据表明 C5aR 及其假定的下游分子 p38 在 LPS 诱导的 DPSCs 成牙分化中起重要作用。本研究强调了补体 C5aR/p38 的调节途径以及在炎症期间提高牙本质再生效率的可能治疗方法。
