School of Stomatology, Shandong Second Medical University, Weifang, China.
Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, China.
J Cell Mol Med. 2024 Feb;28(4):e18143. doi: 10.1111/jcmm.18143.
Nerve growth factor (NGF) and its receptor, tropomyosin receptor kinase A (TrkA), are known to play important roles in the immune and nervous system. However, the effects of NGF on the osteogenic differentiation of dental pulp stem cells (DPSCs) remain unclear. This study aimed to investigate the role of NGF on the osteogenic differentiation of DPSCs in vitro and the underlying mechanisms. DPSCs were cultured in osteogenic differentiation medium containing NGF (50 ng/mL) for 7 days. Then osteogenic-related genes and protein markers were analysed using qRT-PCR and Western blot, respectively. Furthermore, addition of NGF inhibitor and small interfering RNA (siRNA) transfection experiments were used to elucidate the molecular signalling pathway responsible for the process. NGF increased osteogenic differentiation of DPSCs significantly compared with DPSCs cultured in an osteogenic-inducing medium. The NGF inhibitor Ro 08-2750 (10 μM) and siRNA-mediated gene silencing of NGF receptor, TrkA and ERK signalling pathways inhibitor U0126 (10 μM) suppressed osteogenic-related genes and protein markers on DPSCs. Furthermore, our data revealed that NGF-upregulated osteogenic differentiation of DPSCs may be associated with the activation of MEK/ERK signalling pathways via TrkA. Collectively, NGF was capable of promoting osteogenic differentiation of DPSCs through MEK/ERK signalling pathways, which may enhance the DPSCs-mediated bone tissue regeneration.
神经生长因子（NGF）及其受体原肌球蛋白受体激酶 A（TrkA）已知在免疫系统和神经系统中发挥重要作用。然而，NGF 对牙髓干细胞（DPSCs）成骨分化的影响尚不清楚。本研究旨在探讨 NGF 对体外 DPSCs 成骨分化的作用及其潜在机制。将 DPSCs 培养在含有 NGF（50ng/ml）的成骨诱导培养基中 7 天。然后分别通过 qRT-PCR 和 Western blot 分析成骨相关基因和蛋白标志物。此外，还进行了 NGF 抑制剂和小干扰 RNA（siRNA）转染实验，以阐明负责该过程的分子信号通路。与在成骨诱导培养基中培养的 DPSCs 相比，NGF 显著增加了 DPSCs 的成骨分化。NGF 抑制剂 Ro 08-2750（10 μM）和 NGF 受体 TrkA 和 ERK 信号通路抑制剂 U0126（10 μM）的 siRNA 介导基因沉默抑制了 DPSCs 中的成骨相关基因和蛋白标志物。此外，我们的数据表明，NGF 可能通过 TrkA 激活 MEK/ERK 信号通路来上调 DPSCs 的成骨分化。综上所述，NGF 能够通过 MEK/ERK 信号通路促进 DPSCs 的成骨分化，从而增强 DPSCs 介导的骨组织再生。
