ASXL2调节染色质重塑以指导人牙周膜干细胞的成骨和多种细胞命运。

ASXL2 Modulates Chromatin Remodeling to Direct Osteogenesis and Multiple Cell Fate in hPDLSCs.

作者信息

Yang Tianle, Zhou Ying, Han Ruohui, Hu Meilin, Zeng Bo, Shi Hong, Liu Dayong

机构信息

School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology & Hebei Clinical Research Center for Oral Diseases, Shijiazhuang, Hebei Provience, PR China; Department of Endodontics, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin, PR China.

Department of Endodontics, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin, PR China.

出版信息

Int Dent J. 2025 Jul 17;75(5):100900. doi: 10.1016/j.identj.2025.100900.

DOI:10.1016/j.identj.2025.100900

PMID:40680514

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12303053/

Abstract

AIMS

This study investigates the epigenetic role of Additional Sex Combs-Like 2 (ASXL2) in regulating osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), aiming to address limitations in current strategies for oral and maxillofacial tissue regeneration.

METHODS

Lentiviral-mediated ASXL2 knockdown in hPDLSCs was validated by flow cytometry. Functional impacts were assessed through proliferation/apoptosis assays, alkaline phosphatase (ALP) activity, Alizarin Red mineralization, and qPCR/Western blot analyses of osteogenic markers (RUNX2, ALP, COL1A1, OCN). Global histone modification dynamics (H2AK119ub, H3K27me3, H3K4me3) were detected to elucidate epigenetic mechanisms.

RESULTS

ASXL2 depletion enhanced hPDLSC proliferation and reduced apoptosis, but critically impaired osteogenic differentiation, evidenced by suppressed ALP activity and mineralization. Global downregulation of osteogenic markers is correlated with altered chromatin states: decreased activating H3K4me3 and increased repressive H2AK119ub/H3K27me3.

CONCLUSION

ASXL2 modulates the osteogenic competency of hPDLSCs through epigenetic regulation, wherein its loss disrupts transcriptional accessibility by skewing histone modification balance: suppressing H3K4me3-mediated activation while amplifying H2AK119ub/H3K27me3-dependent repression to downregulate specific osteogenic genes.

CLINICAL RELEVANCE

ASXL2 emerges as a pivotal epigenetic target for craniofacial regeneration. Strategic modulation of ASXL2 activity may optimize hPDLSC-based therapies to restore masticatory, pronunciation, and aesthetic functions.

摘要

目的

本研究探讨类额外性梳蛋白2（ASXL2）在调节人牙周膜干细胞（hPDLSCs）成骨分化中的表观遗传作用，旨在解决当前口腔颌面组织再生策略中的局限性。

方法

通过流式细胞术验证慢病毒介导的hPDLSCs中ASXL2的敲低。通过增殖/凋亡检测、碱性磷酸酶（ALP）活性、茜素红矿化以及成骨标志物（RUNX2、ALP、COL1A1、OCN）的qPCR/蛋白质印迹分析评估功能影响。检测整体组蛋白修饰动态变化（H2AK119ub、H3K27me3、H3K4me3）以阐明表观遗传机制。