ArticleAntioxidants & redox signaling2017
Cystathionine γ-Lyase-Hydrogen Sulfide Induces Runt-Related Transcription Factor 2 Sulfhydration, Thereby Increasing Osteoblast Activity to Promote Bone Fracture Healing.
Article in Antioxidants & redox signaling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 60 citations in OpenAlex.
- Harnessing gasotransmitters for orthopaedic infection therapy: Mechanisms and advanced delivery platforms.Bioactive materials · 2027Review
- Elucidating the mechanism of taurine in alleviating osteoarthritis progression based on bioinformatics, machine learning algorithm, and experimental validation.Arthritis research & therapy · 2026Article
- S-sulfhydration: Novel insights into the antioxidant and antiinflammation in age-related diseases.Journal of advanced research · 2026Review
- HFrontiers in cell and developmental biology · 2026Review
- Article
- Association of a Sulfur-Containing Diet and a CTH Polymorphism with Bone Density in the Uyghur Population of China: A Preliminary Study.International journal of general medicine · 2025Article
- The Role of Gasotransmitter-Dependent Signaling Mechanisms in Apoptotic Cell Death in Cardiovascular, Rheumatic, Kidney, and Neurodegenerative Diseases and Mental Disorders.International journal of molecular sciences · 2023Review
- Local delivery of gaseous signaling molecules for orthopedic disease therapy.Journal of nanobiotechnology · 2023Review
- The Role of Hydrogen Sulfide in Plaque Stability.Antioxidants (Basel, Switzerland) · 2022Review
- Reactive sulfur and selenium species in the regulation of bone homeostasis.Free radical biology & medicine · 2022Review
- Targeting Sirt1, AMPK, Nrf2, CK2, and Soluble Guanylate Cyclase with Nutraceuticals: A Practical Strategy for Preserving Bone Mass.International journal of molecular sciences · 2022Review
- A novel fluorescent probe for detecting hydrogen sulfide in osteoblasts during lipopolysaccharide-mediated inflammation under periodontitis.Scientific reports · 2021Article
- The Gasotransmitter Hydrogen Sulfide (HAntioxidants (Basel, Switzerland) · 2021Article
- The Hidden Role of Hydrogen Sulfide Metabolism in Cancer.International journal of molecular sciences · 2021Review
- Core-binding factor beta is required for osteoblast differentiation during fibula fracture healing.Journal of orthopaedic surgery and research · 2021Article
- Association of Hydrogen Sulfide with Femoral Bone Mineral Density in Osteoporosis Patients: A Preliminary Study.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- S-Persulfidation: Chemistry, Chemical Biology, and Significance in Health and Disease.Antioxidants & redox signaling · 2020Review
- Effect of changes in serum levels of endogenous hydrogen sulfide on fracture healing: Study protocol clinical trial (SPIRIT compliant).Medicine · 2020Article
- The role of the gasotransmitter hydrogen sulfide in pathological calcification.British journal of pharmacology · 2020Review
- Hydrogen sulfide inhibits calcification of heart valves; implications for calcific aortic valve disease.British journal of pharmacology · 2020Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsHydrogen sulfide (H2S) plays an essential role in bone formation, in part, by inhibiting osteoclast differentiation, maintaining mesenchymal stem cell osteogenesis ability, or reducing osteoblast injury. We aimed to investigate the role of H2S in osteoblast function and its possible molecular target.
resultsIn this study, we found that cystathionine γ-lyase (CSE) majorly contributed to endogenous H2S production in the primary osteoblast. Overexpressed CSE increased osteoblast differentiation and maturation with higher bone morphogenetic protein 2 and osteopontin expression, alkaline phosphatase activity, and calcium nodule formation; in contrast, knockdown of CSE had opposite effects. Runt-related transcript factor 2 (RUNX2) is required for osteoblast biologic function. CSE-H2S increased nuclear RUNX2 accumulation, DNA binding activity, and target gene transcription. Protein sulfhydration is a common signal by H2S. We confirmed that RUNX2 was also sulfhydrated by H2S. This chemical modification enhanced RUNX2 transactivation, which was blocked by dithiothreitol (DTT, sulfhydration remover). Mutation of two cysteine sites in the runt domain of RUNX2 abolished H2S-induced RUNX2 sulfhydration and transactivation. In a bone -fracture rat model, overexpressed CSE promoted bone healing, which confirmed the effect of CSE-H2S on osteoblasts. INNOVATION: CSE-H2S is a dominant H2S generation system in osteoblasts and promotes osteoblast activity by the RUNX2 pathway, with RUNX2 sulfhydration as a novel transactivation regulation.
conclusionCSE-H2S sulfhydrated RUNX2 enhanced its transactivation and increased osteoblast differentiation and maturation, thereby promoting bone healing. Antioxid. Redox Signal. 27, 742-753.
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