Histone Acetylation in Bone Remodeling: Metabolic Regulation, Lineage-Specific Chromatin Programs, and Therapeutic Implications
4 affiliations
- 1Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, No. 3 East Qingchun Road, Hangzhou 310016, China
- 2College of Athletic Performance, Shanghai University of Sport, No. 399 Changhai Road, Yangpu District, Shanghai 200438, China
- 3Department of Pharmacy, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, No. 261 Huansha Road, Shangcheng District, Hangzhou 310006, China
- 4School of Exercise and Health, Shanghai University of Sport, No. 399 Changhai Road, Yangpu District, Shanghai 200438, China
Abstract
Bone remodeling requires coordinated transcriptional regulation across osteoblasts, osteoclasts, and osteocytes. Histone acetylation connects cellular metabolism to these lineage-specific programs, yet its regulatory effects depend not simply on total cellular acetyl-CoA abundance, but also on metabolic carbon routing, subcellular acetyl-CoA availability, and the targeting of chromatin-modifying enzymes to specific genomic regions. This review examines how these processes shape skeletal-cell differentiation, function, and communication within the bone-remodeling unit. We integrate evidence linking acetyl-CoA metabolism to histone acetylation across skeletal lineages, highlighting the distinct contributions of metabolic substrate utilization, acetylation and deacetylation machinery, and locus-specific chromatin regulation. We further discuss how mechanical loading, aging, inflammation, and metabolic disease reshape these regulatory networks and influence the balance between bone formation and resorption. Particular attention is given to the distinction between metabolic changes and their chromatin consequences, as well as to the experimental approaches needed to resolve acetyl-CoA compartmentalization and trace metabolic carbon into histone acetyl groups. Finally, we evaluate therapeutic opportunities and challenges in targeting metabolic–chromatin pathways while preserving physiological bone remodeling. Integrating metabolic routing, chromatin regulation, and intercellular communication provides a framework for understanding skeletal adaptation and identifying new avenues for therapeutic development.
Related
- Metabolic Remodeling in Peritoneal Dialysis-Associated Peritoneal Fibrosis: Mechanisms, Candidate Metabolic Signatures, and Therapeutic Perspectives
- Chromatin remodeling in bone organoids: from epigenetic regulation to disease modeling and therapeutic translation.
- Gut microbiota-bile acid-immune axis: receptor signaling, metabolic regulation, and therapeutic translation
- Abdominal Obesity, Brain Glymphatic Function, and LH–dlHPC Appetite Regulation: Current Evidence, Potential Links, and Implications for Metabolic Health
- Cross‐Regulation Between DNA Methylation and Circadian Clock Reprogramming in Ovarian Cancer: Mechanistic Insights, Biomarker Potential, and Therapeutic Implications
BibTeX
@article{dong2026histone,
title = {{Histone Acetylation in Bone Remodeling: Metabolic Regulation, Lineage-Specific Chromatin Programs, and Therapeutic Implications}},
author = {Jianhong Dong and Xianji Wei and Yifan Qian and Yiming Qian and Wei Zhang},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211963},
url = {https://www.mdpi.com/2073-4409/15/21/1963},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Histone Acetylation in Bone Remodeling: Metabolic Regulation, Lineage-Specific Chromatin Programs, and Therapeutic Implications
AU - Jianhong Dong
AU - Xianji Wei
AU - Yifan Qian
AU - Yiming Qian
AU - Wei Zhang
PY - 2026
DA - 2026/10/28
JO - Cells
DO - 10.3390/cells15211963
UR - https://www.mdpi.com/2073-4409/15/21/1963
AB - Bone remodeling requires coordinated transcriptional regulation across osteoblasts, osteoclasts, and osteocytes. Histone acetylation connects cellular metabolism to these lineage-specific programs, yet its regulatory effects depend not simply on total cellular acetyl-CoA abundance, but also on metabolic carbon routing, subcellular acetyl-CoA availability, and the targeting of chromatin-modifying enzymes to specific genomic regions. This review examines how these processes shape skeletal-cell differentiation, function, and communication within the bone-remodeling unit. We integrate evidence linking acetyl-CoA metabolism to histone acetylation across skeletal lineages, highlighting the distinct contributions of metabolic substrate utilization, acetylation and deacetylation machinery, and locus-specific chromatin regulation. We further discuss how mechanical loading, aging, inflammation, and metabolic disease reshape these regulatory networks and influence the balance between bone formation and resorption. Particular attention is given to the distinction between metabolic changes and their chromatin consequences, as well as to the experimental approaches needed to resolve acetyl-CoA compartmentalization and trace metabolic carbon into histone acetyl groups. Finally, we evaluate therapeutic opportunities and challenges in targeting metabolic–chromatin pathways while preserving physiological bone remodeling. Integrating metabolic routing, chromatin regulation, and intercellular communication provides a framework for understanding skeletal adaptation and identifying new avenues for therapeutic development.
SN - 2073-4409
ER -