ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Stem Cell Research
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1634945
This article is part of the Research TopicAdvancements in Stem Cell Differentiation and Disease ApplicationsView all 7 articles
Psoralen-Mediated Regulation of Osteogenic Differentiation of Periodontal Ligament Stem Cells: Involvement of the mTOR Pathway
Provisionally accepted
Yujia Wang1Zhaojiang Fu2Jie Yu3Jin Jing2Hongbo Zhang2
Yuanping Hao2Qihang Huang1Ruibin Ma1
Yingjie Xu2*
Yingtao Wu2*- 1Shandong Second Medical University, Weifang, China
- 2Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, China
- 3Zibo Stomatological Hospital, Zibo, China
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Background: Chronic periodontitis is a prevalent inflammatory and destructive oral disease, and its primary treatment is to control the development of inflammation and promote the regeneration of periodontal tissue. Psoralen (Pso) has been shown to promote the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), suggesting its potential as a therapeutic agent for osteogenic regeneration.Methods: Network pharmacology and transcriptomic sequencing were exploited to screen target genes of Pso in PDLSCs, lentiviruses were employed to interfere with the target gene, and RT-qPCR was conducted to assess the expression levels of osteogenesis-related factors. Pso-loaded mesoporous polydopamine (MPDA-Pso) nanoparticles were constructed and evaluated in vitro, and in vivo osteogenesis was assessed in rats with alveolar bone defects.Results: Network pharmacology analysis revealed that the mammalian target of rapamycin (mTOR) was a potential target of Pso, and Pso significantly modulated the expression levels of mTOR in PDLSCs and markedly enhanced osteogenic differentiation. However, Pso did not significantly alter osteogenesis-related genes in PDLSCs after mTOR-inhibitor treatment. We also confirmed that MPDA-Pso nanoparticles promoted the expression of osteogenesis-related genes in PDLSCs; and compared with the control group, observed that the mass of new bone was augmented in the MPDA-Pso group.Pso was shown to promote the osteogenic differentiation of PDLSCs, and we postulate that this differentiation was facilitated in the LPS-induced inflammatory microenvironment via inhibition of the autophagy-related mTOR-signaling pathway. Additionally, the MPDA-Pso nanoparticles we developed promoted osteogenesis.
Keywords: PDLSCs, Psoralen, Osteogenic differentiation, mTOR, Periodontitis
Received: 25 May 2025; Accepted: 27 Jun 2025.
Copyright: © 2025 Wang, Fu, Yu, Jing, Zhang, Hao, Huang, Ma, Xu and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yingjie Xu, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, China
Yingtao Wu, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, China
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