2. Academic Validation
  3. Acetylation of H3K18 activated by p300 promotes osteogenesis in human adipose-derived mesenchymal stem cells

Acetylation of H3K18 activated by p300 promotes osteogenesis in human adipose-derived mesenchymal stem cells

  • Biochem Pharmacol. 2025 Jun:236:116901. doi: 10.1016/j.bcp.2025.116901.
Liping Zeng 1,  Chen Chen 1,  Yafei Xiong 2,  Yinan Liu 1,  Miao Huang 3,  Junsong Ye 4,  Jianing Zhong 5,  Weijie Peng 6
Affiliations

Affiliations

  • 1 School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; Jiangxi Province Key Laboratory of Biomaterials and Biofabrication for Tissue Engineering, Gannan Medical University, Ganzhou 341000, China; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, China.
  • 2 Jiangxi Province Key Laboratory of Biomaterials and Biofabrication for Tissue Engineering, Gannan Medical University, Ganzhou 341000, China; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, China; School of Medical Information Engineering, Gannan Medical University, Ganzhou 341000, China.
  • 3 Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, China.
  • 4 Jiangxi Province Key Laboratory of Biomaterials and Biofabrication for Tissue Engineering, Gannan Medical University, Ganzhou 341000, China; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, China; Subcenter for Stem Cell Clinical Translation, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China.
  • 5 Jiangxi Province Key Laboratory of Biomaterials and Biofabrication for Tissue Engineering, Gannan Medical University, Ganzhou 341000, China; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, China. Electronic address: zhongning_003@163.com.
  • 6 Jiangxi Province Key Laboratory of Biomaterials and Biofabrication for Tissue Engineering, Gannan Medical University, Ganzhou 341000, China; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, China; School of Pharmaceutics, Nanchang Medical College, Nanchang, 330000, China. Electronic address: pengweijie@gmu.edu.cn.
PMID: 40164340 DOI: 10.1016/j.bcp.2025.116901
Abstract

Human adipose-derived mesenchymal stem cells (hAD-MSCs) have garnered significant interest as a viable alternative source of stem cells for applications in bone tissue engineering due to their high and ease availability. At present, the limited studies on potential epigenetic regulatory mechanism in hAD-MSCs greatly hinders its clinical application in bone repair. Histone acetylation has been identified as a critical regulator of the osteogenic differentiation of mesenchymal stem cells (MSCs), with increased levels of histone acetylation sites frequently correlating with enhanced osteogenic differentiation. However, their specific roles in MSCs osteogenesis remain unclear. In this study, we observed a significant up-regulation of H3K18 acetylation (H3K18ac) during the osteogenic induction of hAD-MSCs. This modification was notably enriched in the promoter regions of genes associated with osteogenesis, thereby facilitating osteogenic differentiation. Furthermore, the treatment of histone acetyltransferases p300 inhibitor A-485 in hAD-MSCs resulted in a reduction of H3K18 acetylation levels during the osteogenic differentiation, which corresponded with a diminished osteoblast phenotype and function. These results indicated that p300-mediated acetylation of H3K18 enhances the osteogenic differentiation of hAD-MSCs. It provides a novel insight into understanding the mechanism of osteogenic differentiation of hAD-MSCs and promoting its application in bone tissue engineering.

Keywords

H3K18 acetylation; Osteogenic differentiation; P300; hAD-MSCs.

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