Baishideng Publishing Group
World Journal of Stem Cells
,  volume 17 ,  issue 4

EZH2, via an association with KDM2B, modulates osteogenic differentiation of root apical papillary stem cells

Publication type: Journal Article
Publication date: 2025-04-26
Baishideng Publishing Group
scimago Q1
wos Q2
SJR: 0.996
CiteScore: 6.9
Impact factor: 3.6
ISSN: 19480210
Abstract

BACKGROUND

Stem cells from apical papilla (SCAPs) represent promising candidates for bone regenerative therapies due to their osteogenic potential. However, enhancing their differentiation capacity remains a critical challenge. Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, regulates osteogenesis through epigenetic mechanisms, but its role in SCAPs remains unclear. We hypothesized that EZH2 modulates SCAP osteogenic differentiation via interaction with lysine demethylase 2B (KDM2B), offering a target for therapeutic intervention.

AIM

To investigate the functional role and molecular mechanism of EZH2 in SCAP osteogenic differentiation.

METHODS

SCAPs were isolated from healthy human third molars (n = 6 donors). Osteogenic differentiation was assessed via Alizarin red staining and alkaline phosphatase assays. EZH2 overexpression/knockdown models were established using lentiviral vectors. Protein interactions were analyzed by co-immunoprecipitation, transcriptomic changes via microarray (Affymetrix platform), and chromatin binding by chromatin immunoprecipitation-quantitative polymerase chain reaction. In vivo bone formation was evaluated in immunodeficient mice (n = 8/group) transplanted with SCAPs-hydroxyapatite scaffolds. Data were analyzed using Student’s t -test and ANOVA.

RESULTS

EZH2 overexpression increased osteogenic markers and mineralized nodule formation. In vivo , EZH2-overexpressing SCAPs generated 10% more bone/dentin-like tissue. Co-immunoprecipitation confirmed EZH2-KDM2B interaction, and peptide-mediated disruption of this binding enhanced osteogenesis. Transcriptome analysis identified 1648 differentially expressed genes (971 upregulated; 677 downregulated), with pathway enrichment in Wnt/β-catenin signaling.

CONCLUSION

EZH2 promotes SCAP osteogenesis via antagonistic interaction with KDM2B, and targeted disruption of this axis offers a translatable strategy for bone regeneration.

Found 

Are you a researcher?

Create a profile to get free access to personal recommendations for colleagues and new articles.
Metrics
0
Share
Cite this
GOST |
Cite this
GOST Copy
Xu H. et al. EZH2, via an association with KDM2B, modulates osteogenic differentiation of root apical papillary stem cells // World Journal of Stem Cells. 2025. Vol. 17. No. 4.
GOST all authors (up to 50) Copy
Xu H. L., Wang Y., Yang H., Cao Y., Fan Z. EZH2, via an association with KDM2B, modulates osteogenic differentiation of root apical papillary stem cells // World Journal of Stem Cells. 2025. Vol. 17. No. 4.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.4252/wjsc.v17.i4.103482
UR - https://www.wjgnet.com/1948-0210/full/v17/i4/103482.htm
TI - EZH2, via an association with KDM2B, modulates osteogenic differentiation of root apical papillary stem cells
T2 - World Journal of Stem Cells
AU - Xu, Huan Li
AU - Wang, Yan-Tong
AU - Yang, Haoqing
AU - Cao, Yangyang
AU - Fan, Zhipeng
PY - 2025
DA - 2025/04/26
PB - Baishideng Publishing Group
IS - 4
VL - 17
SN - 1948-0210
ER -
BibTex
Cite this
BibTex (up to 50 authors) Copy
@article{2025_Xu,
author = {Huan Li Xu and Yan-Tong Wang and Haoqing Yang and Yangyang Cao and Zhipeng Fan},
title = {EZH2, via an association with KDM2B, modulates osteogenic differentiation of root apical papillary stem cells},
journal = {World Journal of Stem Cells},
year = {2025},
volume = {17},
publisher = {Baishideng Publishing Group},
month = {apr},
url = {https://www.wjgnet.com/1948-0210/full/v17/i4/103482.htm},
number = {4},
doi = {10.4252/wjsc.v17.i4.103482}
}