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Hydrogen sulfide in bone homeostasis: Mechanisms and therapeutic potential.

Created on 24 Oct 2026

Authors

Botian Tan, Manqing Liu, Deqian Tang, Junbin Wei, Chenxi Sun, Houze Li, Zhengshi Li, Yunyi Xie, Qianmin Ou

Published in

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. Volume 204. Pages 119993. Oct 22, 2026. Epub Oct 22, 2026.

Abstract

Hydrogen sulfide (H₂S), as an endogenous gaseous signaling molecule, plays a central and complex regulatory role in maintaining bone homeostasis. This review summarizes the current evidence that H₂S participates in skeletal remodeling through coordinated regulation of osteoblast-lineage cells, osteoclasts, macrophage-mediated immune responses, and metabolic stress adaptation. Rather than acting as a simple unidirectional bone-protective factor, H₂S exerts context-dependent effects that are shaped by local concentration, release kinetics, cellular source, disease state, and the surrounding immune-metabolic microenvironment. These properties allow H₂S to serve as a dynamic mediator linking cellular function, microenvironmental remodeling, and skeletal homeostasis. With the development of sustained-release donors, microenvironment-responsive biomaterials, enzyme-modulating approaches, and combination strategies, H₂S-targeted interventions have become a promising direction for bone repair and regeneration. This review integrates cellular mechanisms, disease-associated H₂S synthesis disorders, and translational strategies to clarify the context-dependent role of H₂S in bone homeostasis and to provide perspectives for precision skeletal repair.

PMID:
42913246
Bibliographic data and abstract were imported from PubMed on 24 Oct 2026.

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