PMID- 29908298
OWN - NLM
STAT- MEDLINE
DCOM- 20190722
LR  - 20230928
IS  - 1873-2763 (Electronic)
IS  - 8756-3282 (Print)
IS  - 1873-2763 (Linking)
VI  - 114
DP  - 2018 Sep
TI  - Hydrogen sulfide epigenetically mitigates bone loss through OPG/RANKL regulation 
      during hyperhomocysteinemia in mice.
PG  - 90-108
LID - S8756-3282(18)30241-2 [pii]
LID - 10.1016/j.bone.2018.06.009 [doi]
AB  - Hydrogen sulfide (H(2)S) is a novel gasotransmitter produced endogenously in 
      mammalian cells, which works by mediating diverse physiological functions. An 
      imbalance in H(2)S metabolism is associated with defective bone homeostasis. 
      However, it is unknown whether H(2)S plays any epigenetic role in bone loss 
      induced by hyperhomocysteinemia (HHcy). We demonstrate that diet-induced HHcy, a 
      mouse model of metabolite induced osteoporosis, alters homocysteine metabolism by 
      decreasing plasma levels of H(2)S. Treatment with NaHS (H(2)S donor), normalizes 
      the plasma level of H(2)S and further alleviates HHcy induced trabecular bone 
      loss and mechanical strength. Mechanistic studies have shown that DNMT1 
      expression is higher in the HHcy condition. The data show that activated 
      phospho-JNK binds to the DNMT1 promoter and causes epigenetic DNA 
      hyper-methylation of the OPG gene. This leads to activation of RANKL expression 
      and mediates osteoclastogenesis. However, administration of NaHS could prevent 
      HHcy induced bone loss. Therefore, H(2)S could be used as a novel therapy for 
      HHcy mediated bone loss.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Behera, Jyotirmaya
AU  - Behera J
AD  - Department of Physiology, School of Medicine, University of Louisville, 
      Louisville, KY 40292, USA.
FAU - George, Akash K
AU  - George AK
AD  - Department of Physiology, School of Medicine, University of Louisville, 
      Louisville, KY 40292, USA.
FAU - Voor, Michael J
AU  - Voor MJ
AD  - Departments of Orthopaedic Surgery and Bioengineering, School of Medicine and 
      Speed School of Engineering, University of Louisville, Louisville, KY 40292, USA.
FAU - Tyagi, Suresh C
AU  - Tyagi SC
AD  - Department of Physiology, School of Medicine, University of Louisville, 
      Louisville, KY 40292, USA.
FAU - Tyagi, Neetu
AU  - Tyagi N
AD  - Department of Physiology, School of Medicine, University of Louisville, 
      Louisville, KY 40292, USA. Electronic address: n0tyag01@louisville.edu.
LA  - eng
GR  - R01 AR067667/AR/NIAMS NIH HHS/United States
GR  - R01 HL107640/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180613
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (Osteoprotegerin)
RN  - 0 (RANK Ligand)
RN  - 0 (Tnfrsf11b protein, mouse)
RN  - 0 (Tnfsf11 protein, mouse)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Bone Diseases, Metabolic/drug therapy/genetics/*metabolism
MH  - Epigenomics/*methods
MH  - Female
MH  - Hydrogen Sulfide/pharmacology/*therapeutic use
MH  - Hyperhomocysteinemia/drug therapy/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Osteogenesis/drug effects/physiology
MH  - Osteoprotegerin/genetics/*metabolism
MH  - RANK Ligand/genetics/*metabolism
PMC - PMC6084464
MID - NIHMS976649
OTO - NOTNLM
OT  - Bone loss
OT  - DNA methyltransferase
OT  - Epigenetic DNA methylation
OT  - Osteoblastogenesis
OT  - Osteoclastogenesis
COIS- Conflict of interest All authors declare no conflict of interest.
EDAT- 2018/06/17 06:00
MHDA- 2019/07/23 06:00
PMCR- 2019/09/01
CRDT- 2018/06/17 06:00
PHST- 2018/01/16 00:00 [received]
PHST- 2018/06/06 00:00 [revised]
PHST- 2018/06/12 00:00 [accepted]
PHST- 2018/06/17 06:00 [pubmed]
PHST- 2019/07/23 06:00 [medline]
PHST- 2018/06/17 06:00 [entrez]
PHST- 2019/09/01 00:00 [pmc-release]
AID - S8756-3282(18)30241-2 [pii]
AID - 10.1016/j.bone.2018.06.009 [doi]
PST - ppublish
SO  - Bone. 2018 Sep;114:90-108. doi: 10.1016/j.bone.2018.06.009. Epub 2018 Jun 13.