PMID- 30912146
OWN - NLM
STAT- MEDLINE
DCOM- 20200526
LR  - 20211208
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 234
IP  - 10
DP  - 2019 Aug
TI  - Hydrogen sulfide attenuates homocysteine-induced osteoblast dysfunction by 
      inhibiting mitochondrial toxicity.
PG  - 18602-18614
LID - 10.1002/jcp.28498 [doi]
AB  - 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 (H(2) 
      S) has potent antioxidant, anti-inflammatory, and antiapoptotic effects. In this 
      study, we hypothesized that the H(2) 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 H(2) 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 H(2) S level and expression of the cystathionine 
      beta-synthase/Cystathionine gamma-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.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Zhai, Yuankun
AU  - Zhai Y
AUID- ORCID: 0000-0001-8156-1368
AD  - Department of Physiology, School of Medicine, University of Louisville, 
      Louisville, Kentucky.
FAU - Behera, Jyotirmaya
AU  - Behera J
AD  - Department of Physiology, School of Medicine, University of Louisville, 
      Louisville, Kentucky.
FAU - Tyagi, Suresh C
AU  - Tyagi SC
AUID- ORCID: 0000-0002-4574-4850
AD  - Department of Physiology, School of Medicine, University of Louisville, 
      Louisville, Kentucky.
FAU - Tyagi, Neetu
AU  - Tyagi N
AUID- ORCID: 0000-0003-0285-5072
AD  - Department of Physiology, School of Medicine, University of Louisville, 
      Louisville, Kentucky.
LA  - eng
GR  - R01 AR067667/AR/NIAMS NIH HHS/United States
GR  - R01 AR071789/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190325
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Reactive Oxygen Species)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Calcification, Physiologic/drug effects
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Homocysteine/*pharmacology
MH  - Hydrogen Sulfide/*pharmacology
MH  - Mice, Inbred C57BL
MH  - Mitochondria/drug effects/metabolism/*pathology
MH  - Osteoblasts/drug effects/metabolism/*pathology
MH  - Osteogenesis/drug effects
MH  - Oxidative Stress/drug effects
MH  - Reactive Oxygen Species/metabolism
PMC - PMC6719545
MID - NIHMS1048244
OTO - NOTNLM
OT  - hydrogen sulfide
OT  - methionine
OT  - mitochondria
OT  - osteoblast
OT  - oxidative stress
COIS- CONFLICT OF INTERESTS The authors declare that there are no conflict of 
      interests.
EDAT- 2019/03/27 06:00
MHDA- 2020/05/27 06:00
PMCR- 2019/09/03
CRDT- 2019/03/27 06:00
PHST- 2018/07/17 00:00 [received]
PHST- 2019/02/12 00:00 [revised]
PHST- 2019/02/14 00:00 [accepted]
PHST- 2019/03/27 06:00 [pubmed]
PHST- 2020/05/27 06:00 [medline]
PHST- 2019/03/27 06:00 [entrez]
PHST- 2019/09/03 00:00 [pmc-release]
AID - 10.1002/jcp.28498 [doi]
PST - ppublish
SO  - J Cell Physiol. 2019 Aug;234(10):18602-18614. doi: 10.1002/jcp.28498. Epub 2019 
      Mar 25.