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World J Stem Cells. Sep 26, 2025; 17(9): 109662
Published online Sep 26, 2025. doi: 10.4252/wjsc.v17.i9.109662
Post-translational modifications in osteogenic differentiation of oral-derived stem cells: Mechanisms and clinical implications
Zhuo-Jin Shi, Wei Liu
Zhuo-Jin Shi, School/Hospital of Stomatology, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
Wei Liu, Department of Oral Medicine, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Author contributions: Shi ZJ conducted literature review and drafted the manuscript; Liu W conceptualized the study, provided critical revisions, and supervised the overall work.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei Liu, DDS, Associate Chief Physician, Department of Oral Medicine, The Second Affiliated Hospital Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China. liuwei1982@zju.edu.cn
Received: May 18, 2025
Revised: June 22, 2025
Accepted: August 13, 2025
Published online: September 26, 2025
Processing time: 129 Days and 21.3 Hours
Abstract

Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix, with oral-derived stem cells playing a significant role in this process. Various post-translational modifications (PTMs), such as phosphorylation, acetylation, methylation, and glycosylation, regulate osteogenic differentiation (OD). These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix. While the molecular mechanisms behind OD are increasingly understood, many questions remain, particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation. Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases. This review summarizes the role of PTMs in the OD of oral-derived stem cells, discusses their clinical applications, and suggests future research directions.

Keywords: Oral-derived stem cells; Post-translational modifications; Osteogenic differentiation; Bone regeneration; Signaling pathways; Clinical translation

Core Tip: This review clarifies how post-translational modifications (PTMs), including phosphorylation, acetylation, methylation, and lactylation, dynamically modulate the osteogenic differentiation of oral-derived stem cells (ODSCs) under inflammatory or hypoxic conditions. We highlight PTMs as essential molecular switches integrating extracellular signals with transcriptional and epigenetic mechanisms to facilitate bone regeneration. Emerging therapeutic strategies - including histone deacetylase inhibitors, extracellular vesicle-based delivery, and metabolic-epigenetic crosstalk modulation - are proposed to improve ODSCs efficacy in osteoporosis and periodontitis. This review clarifies the PTMs “regulatory code” in ODSCs, connecting mechanistic insights to clinical translation while addressing unresolved challenges in precision regenerative medicine.