Hydrogen Sulfide in Musculoskeletal Diseases: Molecular Mechanisms and Therapeutic Opportunities

Significance: Musculoskeletal diseases seriously affect global health, but their importance is greatly underestimated. These diseases often afflict the elderly, leading to disability, paralysis, and other complications. Hydrogen sulfide (H₂S) plays an important role in the occurrence and development of musculoskeletal diseases, which may have potential therapeutic significance for these diseases. Recent Advances: Recently, it has been found that many musculoskeletal diseases, such as osteoporosis, periodontitis, muscle atrophy, muscle ischemia-reperfusion injury, muscle contraction under high fever, arthritis, and disc herniation, can be alleviated by treatment with H₂S. H₂S may be conducive to the development of multiple myeloma. The mechanism of action of H₂S in the musculoskeletal system has been partly elucidated. A variety of H₂S donors and nano-delivery systems provide promising prospects for H₂S-based therapies. Critical Issues: Related research remains at the level of cell or animal experiments, but clinical research is lacking. The roles of H₂S in more musculoskeletal disorders remain largely unknown. The serious consequences of musculoskeletal diseases have not been widely concerned. Targeted delivery of H₂S remains a challenging task in musculoskeletal diseases. Future Directions: Develop therapeutic drugs for musculoskeletal diseases based on H₂S and test their safety, efficacy, and tolerance. Explore the combination of current drugs for musculoskeletal diseases with H₂S-releasing components to improve the therapeutic efficacy and avoid side effects. Carry out relevant clinical trials to verify the possibility of its widespread use. Antioxid. Redox Signal. 42, 321-340.