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Hydrogen sulfide attenuates homocysteine-induced osteoblast dysfunction by inhibiting mitochondrial toxicity.
J Cell Physiol. 2019 08; 234(10):18602-18614.JC

Abstract

Homocysteine (Hcy) is detrimental to bone health in a mouse model of diet-induced hyperhomocysteinemia (HHcy). However, little is known about Hcy-mediated osteoblast dysfunction via mitochondrial oxidative damage. Hydrogen sulfide (H2 S) has potent antioxidant, anti-inflammatory, and antiapoptotic effects. In this study, we hypothesized that the H2 S mediated recovery of osteoblast dysfunction by maintaining mitochondrial biogenesis in Hcy-treated osteoblast cultures in vitro. MC3T3-E1 osteoblastic cells were exposed to Hcy treatment in the presence or absence of an H2 S donor (NaHS). Cell viability, osteogenic differentiation, reactive oxygen species (ROS) production were determined. Mitochondrial DNA copy number, adenosine triphosphate (ATP) production, and oxygen consumption were also measured. Our results demonstrated that administration of Hcy increases the intracellular Hcy level and decreases intracellular H2 S level and expression of the cystathionine β-synthase/Cystathionine γ-lyase system, thereby inhibiting osteogenic differentiation. Pretreatment with NaHS attenuated Hcy-induced mitochondrial toxicity (production of total ROS and mito-ROS, ratio of mitochondrial fission (DRP-1)/fusion (Mfn-2)) and restored ATP production and mitochondrial DNA copy numbers as well as oxygen consumption in the osteoblast as compared with the control, indicating its protective effects against Hcy-induced mitochondrial toxicity. In addition, NaHS also decreased the release of cytochrome c from the mitochondria to the cytosol, which induces cell apoptosis. Finally, flow cytometry confirmed that NaHS can rescue cells from apoptosis induced by Hcy. Our studies strongly suggest that NaHS has beneficial effects on mitochondrial toxicity, and could be developed as a potential therapeutic agent against HHcy-induced mitochondrial dysfunction in cultured osteoblasts in vitro.

Authors+Show Affiliations

Department of Physiology, School of Medicine, University of Louisville, Louisville, Kentucky.Department of Physiology, School of Medicine, University of Louisville, Louisville, Kentucky.Department of Physiology, School of Medicine, University of Louisville, Louisville, Kentucky.Department of Physiology, School of Medicine, University of Louisville, Louisville, Kentucky.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30912146

Citation

Zhai, Yuankun, et al. "Hydrogen Sulfide Attenuates Homocysteine-induced Osteoblast Dysfunction By Inhibiting Mitochondrial Toxicity." Journal of Cellular Physiology, vol. 234, no. 10, 2019, pp. 18602-18614.
Zhai Y, Behera J, Tyagi SC, et al. Hydrogen sulfide attenuates homocysteine-induced osteoblast dysfunction by inhibiting mitochondrial toxicity. J Cell Physiol. 2019;234(10):18602-18614.
Zhai, Y., Behera, J., Tyagi, S. C., & Tyagi, N. (2019). Hydrogen sulfide attenuates homocysteine-induced osteoblast dysfunction by inhibiting mitochondrial toxicity. Journal of Cellular Physiology, 234(10), 18602-18614. https://doi.org/10.1002/jcp.28498
Zhai Y, et al. Hydrogen Sulfide Attenuates Homocysteine-induced Osteoblast Dysfunction By Inhibiting Mitochondrial Toxicity. J Cell Physiol. 2019;234(10):18602-18614. PubMed PMID: 30912146.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydrogen sulfide attenuates homocysteine-induced osteoblast dysfunction by inhibiting mitochondrial toxicity. AU - Zhai,Yuankun, AU - Behera,Jyotirmaya, AU - Tyagi,Suresh C, AU - Tyagi,Neetu, Y1 - 2019/03/25/ PY - 2018/07/17/received PY - 2019/02/12/revised PY - 2019/02/14/accepted PY - 2019/3/27/pubmed PY - 2020/5/27/medline PY - 2019/3/27/entrez KW - hydrogen sulfide KW - methionine KW - mitochondria KW - osteoblast KW - oxidative stress SP - 18602 EP - 18614 JF - Journal of cellular physiology JO - J. Cell. Physiol. VL - 234 IS - 10 N2 - Homocysteine (Hcy) is detrimental to bone health in a mouse model of diet-induced hyperhomocysteinemia (HHcy). However, little is known about Hcy-mediated osteoblast dysfunction via mitochondrial oxidative damage. Hydrogen sulfide (H2 S) has potent antioxidant, anti-inflammatory, and antiapoptotic effects. In this study, we hypothesized that the H2 S mediated recovery of osteoblast dysfunction by maintaining mitochondrial biogenesis in Hcy-treated osteoblast cultures in vitro. MC3T3-E1 osteoblastic cells were exposed to Hcy treatment in the presence or absence of an H2 S donor (NaHS). Cell viability, osteogenic differentiation, reactive oxygen species (ROS) production were determined. Mitochondrial DNA copy number, adenosine triphosphate (ATP) production, and oxygen consumption were also measured. Our results demonstrated that administration of Hcy increases the intracellular Hcy level and decreases intracellular H2 S level and expression of the cystathionine β-synthase/Cystathionine γ-lyase system, thereby inhibiting osteogenic differentiation. Pretreatment with NaHS attenuated Hcy-induced mitochondrial toxicity (production of total ROS and mito-ROS, ratio of mitochondrial fission (DRP-1)/fusion (Mfn-2)) and restored ATP production and mitochondrial DNA copy numbers as well as oxygen consumption in the osteoblast as compared with the control, indicating its protective effects against Hcy-induced mitochondrial toxicity. In addition, NaHS also decreased the release of cytochrome c from the mitochondria to the cytosol, which induces cell apoptosis. Finally, flow cytometry confirmed that NaHS can rescue cells from apoptosis induced by Hcy. Our studies strongly suggest that NaHS has beneficial effects on mitochondrial toxicity, and could be developed as a potential therapeutic agent against HHcy-induced mitochondrial dysfunction in cultured osteoblasts in vitro. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/30912146/Hydrogen_sulfide_attenuates_homocysteine_induced_osteoblast_dysfunction_by_inhibiting_mitochondrial_toxicity_ DB - PRIME DP - Unbound Medicine ER -