PMID- 21469179
OWN - NLM
STAT- MEDLINE
DCOM- 20111010
LR  - 20220408
IS  - 1554-527X (Electronic)
IS  - 0736-0266 (Print)
IS  - 0736-0266 (Linking)
VI  - 29
IP  - 10
DP  - 2011 Oct
TI  - Homocysteine mediated decrease in bone blood flow and remodeling: role of folic 
      acid.
PG  - 1511-6
LID - 10.1002/jor.21415 [doi]
AB  - Deficiencies in folate lead to increased serum concentrations of homocysteine 
      (Hcy), which is known as hyperhomocysteinemia (HHcy), is associated with bone 
      disorders. Although, Hcy accumulates collagen in bone and contribute to decrease 
      in bone strength. The mechanism of Hcy induced bone loss and remodeling is 
      unclear. Therefore, the present study was aimed to determine the role of folic 
      acid (FA) in genetically HHcy-associated decrease in bone blood flow and 
      remodeling. Wild type (WT) and cystathionine-beta-synthase heterozygous (CBS+/-) 
      mice were used in this study and supplemented with or without FA (300 mg/kg, Hcy 
      reducing agent) in drinking water for 6 weeks. The tibial bone blood flow was 
      measured by laser Doppler and ultrasonic flow probe method. The tibial bone 
      density (BD) was assessed by dual energy X-ray absorptiometry. The bone 
      homogenates were analyzed for oxidative stress, NOX-4 as oxidative marker and 
      thioredoxin-1 (Trx-1) as anti-oxidant marker, bone remodeling (MMP-9) and 
      bio-availability of nitric oxide (eNOS/iNOS/NO) by Western blot method. The 
      results suggested that there was decrease in tibial blood flow in CBS+/- mice. 
      The BD was also reduced in CBS+/- mice. There was an increase in NOX-4, iNOS, 
      MMP-9 protein as well as MMP-9 activity in CBS+/- mice and decrease in Trx-1, 
      eNOS protein levels, in part by decreasing NO bio-availability in CBS+/- mice. 
      Interestingly, these effects were ameliorated by FA and suggested that FA 
      supplementation may have therapeutic potential against genetically HHcy induced 
      bone loss.
CI  - Copyright (c) 2011 Orthopaedic Research Society.
FAU - Tyagi, Neetu
AU  - Tyagi N
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, Kentucky 40202, USA. n0tyag01@louisville.edu
FAU - Kandel, Madhavi
AU  - Kandel M
FAU - Munjal, Charu
AU  - Munjal C
FAU - Qipshidze, Natia
AU  - Qipshidze N
FAU - Vacek, Jonathan C
AU  - Vacek JC
FAU - Pushpakumar, Sathnur B
AU  - Pushpakumar SB
FAU - Metreveli, Naria
AU  - Metreveli N
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - R01 HL071010/HL/NHLBI NIH HHS/United States
GR  - R01 NS051568/NS/NINDS NIH HHS/United States
GR  - HL-71010/HL/NHLBI NIH HHS/United States
GR  - NS-51568/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110405
PL  - United States
TA  - J Orthop Res
JT  - Journal of orthopaedic research : official publication of the Orthopaedic 
      Research Society
JID - 8404726
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.35 (Mmp9 protein, mouse)
SB  - IM
MH  - Animals
MH  - Bone Density
MH  - *Bone Remodeling
MH  - Folic Acid/*physiology
MH  - Homocysteine/*physiology
MH  - Hyperhomocysteinemia/*complications
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Nitric Oxide/metabolism
MH  - Osteoporosis/*etiology
MH  - Oxidative Stress
MH  - Regional Blood Flow
MH  - Tibia/blood supply
MH  - Tibial Arteries/physiology
PMC - PMC3583304
MID - NIHMS281289
EDAT- 2011/04/07 06:00
MHDA- 2011/10/11 06:00
PMCR- 2013/02/27
CRDT- 2011/04/07 06:00
PHST- 2010/11/03 00:00 [received]
PHST- 2011/02/28 00:00 [accepted]
PHST- 2011/04/07 06:00 [entrez]
PHST- 2011/04/07 06:00 [pubmed]
PHST- 2011/10/11 06:00 [medline]
PHST- 2013/02/27 00:00 [pmc-release]
AID - 10.1002/jor.21415 [doi]
PST - ppublish
SO  - J Orthop Res. 2011 Oct;29(10):1511-6. doi: 10.1002/jor.21415. Epub 2011 Apr 5.