title: Activation of AMPK participates hydrogen sulfide-induced cyto-protective effect against dexamethasone in osteoblastic MC3T3-E1 cells.
abstract: Long-time glucocorticoids (GCs) usage causes osteoporosis. In the present study, we explored the potential role of hydrogen sulfide (H2S) against dexamethasone (Dex)-induced osteoblast cell damage, and focused on the underlying mechanisms. We showed that two H2S-producing enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), were significantly downregulated in human osteonecrosis tissues as well as in Dex-treated osteoblastic MC3T3-E1 cells. H2S donor NaHS as well as the CBS activator S-adenosyl-l-methionine (SAM) inhibited Dex-induced viability reduction, death and apoptosis in MC3T3-E1 cells. NaHS activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling, which participated its cyto-protective activity. AMPK inhibition by its inhibitor (compound C) or reduction by targeted-shRNA suppressed its pro-survival activity against Dex in MC3T3-E1 cells. Further, we found that NaHS inhibited Dex-mediated reactive oxygen species (ROS) production and ATP depletion. Such effects by NaHS were again inhibited by compound C and AMPKα1-shRNA. In summary, we show that H2S inhibits Dex-induced osteoblast damage through activation of AMPK signaling. H2S signaling might be further investigated as a novel target for anti-osteoporosis treatment.
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital of Medical College of Zhejiang University, Hangzhou, Zhejiang 310016, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital of Medical College of Zhejiang University, Hangzhou, Zhejiang 310016, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital of Medical College of Zhejiang University, Hangzhou, Zhejiang 310016, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital of Medical College of Zhejiang University, Hangzhou, Zhejiang 310016, China.
authors.forename: Yi-lei
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital of Medical College of Zhejiang University, Hangzhou, Zhejiang 310016, China.
authors.forename: Jian-jun
authors.initials: JJ
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital of Medical College of Zhejiang University, Hangzhou, Zhejiang 310016, China. Electronic address: zhejiangpeihua163@163.com.
authors.forename: Pei-hua
authors.initials: PH
authors.lastname: Shi
mesh_terms: D016475:3T3 Cells; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010020:Osteonecrosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D003907:Dexamethasone; D000255:Adenosine Triphosphate; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: AMPK and oxidative stress; Dexamethasone; Hydrogen sulfide; Osteoporosis