Research Paper Volume 11, Issue 18 pp 7537—7552
Hydrogen sulfide is a novel regulator implicated in glucocorticoids-inhibited bone formation
- 1 Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
- 2 Department of Orthopedic Surgery, The 72nd Military Hospital of PLA, Huzhou, China
- 3 Department of Orthopedic Surgery, Chinese PLA General Hospital, Beijing, China
- 4 Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Received: February 16, 2019 Accepted: September 5, 2019 Published: September 16, 2019https://doi.org/10.18632/aging.102269
How to Cite
Copyright © 2019 Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 3.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Glucocorticoids contribute to the increased incidence of secondary osteoporosis. Hydrogen sulfide (H2S) is a gasotransmitter and plays an essential role in bone metabolism. In this study, we investigated the therapeutic effects of H2S on glucocorticoid-induced osteoporosis (GIO). We found that dexamethasone (Dex) decreased serum H2S and two key H2S-generating enzymes in the bone marrow in vivo, cystathione b-synthase and cystathione g-lyase. Treatment of H2S-donor GYY4137 in rat significantly relieved the inhibitory effect of Dex on bone formation. Dex inhibited osteoblasts proliferation and osteogenic differentiation and decreased the expressions of the two H2S-generating enzymes. Further investigation showed that H2S was involved in Dex-mediated osteoblasts proliferation, differentiation, and apoptosis. Mechanistically, GYY4137 promoted osteoblastogenesis by activating Wnt signaling through increased production of the Wnt ligands. In comparison, the blockage of Wnt/β-catenin signaling pathway significantly alleviated the effect of H2S on osteoblasts. In conclusion, the restoration of H2S levels is a potential novel therapeutic approach for GIO.