title: Hydrogen sulfide protects MC3T3-E1 osteoblastic cells against H2O2-induced oxidative damage-implications for the treatment of osteoporosis.
abstract: Osteoporosis is a bone disease that leads to an increased risk of fracture. Oxidative damage is an important contributor to the morphological and functional changes in the development of osteoporosis. We found in this study that hydrogen sulfide (H2S), a novel endogenous gaseous mediator, protected MC3T3-E1 osteoblastic cells against hydrogen peroxide (H2O2)-induced oxidative injury. NaHS, an H2S donor, increased cell viability and reduced cell apoptosis caused by H2O2. NaHS also stimulated osteoblast proliferation by enhancing both transcription and activity of alkaline phosphatase in MC3T3-E1 osteoblastic cells. Moreover, treatment with NaHS stimulated the transcriptional level of osteocalcin, the main bone matrix protein, and the protein expression of collagen, a major constituent of bone tissue. The above effects were mediated by the antioxidant effect of H2S. NaHS reversed the reduced superoxide dismutase activity, decreased reactive oxygen species production, and suppressed NADPH oxidase activity in H2O2-treated osteoblasts. In addition, NaHS treatment also produced anti-inflammatory effects via inhibition of the production of nitric oxide and TNF-α, suggesting an anti-inflammatory effect of H2S. Cell viability and Western blotting analysis demonstrated that the protective effects of H2S were mediated by p38 and ERK1/2 MAPKs. In conclusion, H2S protects osteoblastic cells against oxidative stress-induced cell injury and suppression of proliferation and differentiation via a MAPK (p38 and ERK1/2)-dependent mechanism. Our findings suggest that H2S may have a potentially therapeutic value for osteoporosis.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore.
authors.forename: Zhong-Shi
authors.initials: ZS
authors.lastname: Xu
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Wang
authors.forename: De-Ming
authors.initials: DM
authors.lastname: Xiao
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Hu
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Wu
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Bian
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D006861:Hydrogen Peroxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D006862:Hydrogen Sulfide