Hydrogen sulfide in bone homeostasis: Mechanisms and therapeutic potential - 07/11/26
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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
H₂S in bone homeostasis: mechanisms, microenvironment, and therapeutic potential. This graphical abstract summarizes the context-dependent regulatory role of hydrogen sulfide (H₂S) in bone homeostasis. The left segment illustrates endogenous H₂S biosynthesis through cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST). The second segment depicts the effects of H₂S on osteogenic cells, highlighting RUNX2-, Wnt/β-catenin-, and Ca²⁺-dependent signaling and the resulting enhancement of mineralization and osteogenesis. The third segment illustrates the bidirectional regulation of osteoclasts, showing that controlled or sustained H₂S exposure may suppress osteoclastogenesis and bone resorption, whereas pathological or excessive H₂S exposure may promote osteoclastogenesis and bone resorption. The fourth segment summarizes the influence of the immune and metabolic bone microenvironment, including macrophage responses, inflammatory signaling, extracellular vesicle-mediated communication, and oxidative stress, which collectively shape H₂S responses. The right segment highlights H₂S-targeted therapeutic strategies, including H₂S donors, responsive biomaterials/hydrogels, and H₂S-preconditioned extracellular vesicles or mesenchymal stem cells, ultimately aiming to achieve controlled H₂S delivery and promote bone repair and regeneration.
H₂S in bone homeostasis: mechanisms, microenvironment, and therapeutic potential. This graphical abstract summarizes the context-dependent regulatory role of hydrogen sulfide (H₂S) in bone homeostasis. The left segment illustrates endogenous H₂S biosynthesis through cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST). The second segment depicts the effects of H₂S on osteogenic cells, highlighting RUNX2-, Wnt/β-catenin-, and Ca²⁺-dependent signaling and the resulting enhancement of mineralization and osteogenesis. The third segment illustrates the bidirectional regulation of osteoclasts, showing that controlled or sustained H₂S exposure may suppress osteoclastogenesis and bone resorption, whereas pathological or excessive H₂S exposure may promote osteoclastogenesis and bone resorption. The fourth segment summarizes the influence of the immune and metabolic bone microenvironment, including macrophage responses, inflammatory signaling, extracellular vesicle-mediated communication, and oxidative stress, which collectively shape H₂S responses. The right segment highlights H₂S-targeted therapeutic strategies, including H₂S donors, responsive biomaterials/hydrogels, and H₂S-preconditioned extracellular vesicles or mesenchymal stem cells, ultimately aiming to achieve controlled H₂S delivery and promote bone repair and regeneration. Le texte complet de cet article est disponible en PDF.
Highlights |
• | H 2 S regulates bone homeostasis in a context-dependent manner. |
• | H 2 S coordinates osteogenesis, osteoclastogenesis and osteoimmunity. |
• | Metabolic and inflammatory microenvironments shape H 2 S signaling. |
• | Advanced H 2 S delivery systems improve bone repair and regeneration. |
• | Precision H 2 S-based therapies offer new opportunities for skeletal repair. |
Keywords : Hydrogen sulfide, Bone homeostasis, Macrophage polarization, Gaseous signaling molecules
Plan
Vol 204
Article 119993- novembre 2026 Retour au numéro
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