Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital, Southwest Medical University, Yunfenglu 10, Luzhou, 646000, China.
Luzhou Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Xianglinlu 1, Luzhou, 646000, China.
Hum Cell. 2024 Nov;37(6):1649-1662. doi: 10.1007/s13577-024-01123-5. Epub 2024 Aug 27.
As periodontal progenitor cells, human dental follicle stem cells (hDFCs) play an important role in regenerative medicine research. Mechanical stimuli exert different regulatory effects on various functions of stem cells. Mechanosensitive ion channels can perceive and transmit mechanical signals. Piezo1 is a novel mechanosensitive cation channel dominated by Ca permeation. The yes-associated protein 1 (YAP1) and mitogen-activated protein kinase (MAPK) pathways can respond to mechanical stimuli and play important roles in cell growth, differentiation, apoptosis, and cell cycle regulation. In this study, we demonstrated that Piezo1 was able to transduce cyclic tension stress (CTS) and promote the osteogenic differentiation of hDFCs by applying CTS of 2000 μstrain to hDFCs. Further investigation of this mechanism revealed that CTS activated Piezo1 in hDFCs and resulted in increased levels of intracellular Ca, YAP1 nuclear translocation, and phosphorylated protein expression levels of extracellular signalling-associated kinase 1/2 (ERK 1/2) and Jun amino-terminal kinase 1/2/3 (JNK 1/3) of the MAPK pathway family. However, when Piezo1 was knocked down in the hDFCs, all these increases disappeared. We conclude that CTS activates Piezo1 expression and promotes its osteogenesis via Ca/YAP1/MAPK in hDFCs. Appropriate mechanical stimulation promotes the osteogenic differentiation of hDFCs via Piezo1. Targeting Piezo1 may be an effective strategy to regulate the osteogenic differentiation of hDFCs, contributing to MSC-based therapies in the field of bone tissue engineering.
作为牙周祖细胞，人牙囊干细胞（hDFCs）在再生医学研究中发挥着重要作用。机械刺激对干细胞的各种功能具有不同的调节作用。机械敏感离子通道可以感知和传递机械信号。Piezo1 是一种新型的机械敏感阳离子通道，以 Ca 渗透为主导。Yes 相关蛋白 1（YAP1）和丝裂原活化蛋白激酶（MAPK）途径可以响应机械刺激，并在细胞生长、分化、凋亡和细胞周期调控中发挥重要作用。在这项研究中，我们证明了 Piezo1 能够通过对 hDFCs 施加 2000μstrain 的循环张力刺激（CTS）来传递 CTS，并促进 hDFCs 的成骨分化。进一步研究该机制表明，CTS 激活了 hDFCs 中的 Piezo1，导致细胞内 Ca 水平升高，YAP1 核易位，并增加了细胞外信号相关激酶 1/2（ERK 1/2）和丝裂原活化蛋白激酶（MAPK）途径家族的 Jun 氨基末端激酶 1/2/3（JNK 1/3）的磷酸化蛋白表达水平。然而，当 hDFCs 中的 Piezo1 被敲低时，所有这些增加都消失了。我们得出结论，CTS 通过 hDFCs 中的 Ca/YAP1/MAPK 激活 Piezo1 表达并促进其成骨作用。适当的机械刺激通过 Piezo1 促进 hDFCs 的成骨分化。靶向 Piezo1 可能是调节 hDFCs 成骨分化的有效策略，有助于骨组织工程领域的 MSC 治疗。
