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COX-2 is necessary for venous ligation-mediated bone adaptation in mice

Stevens, H Y; Meays, D R; Yeh, J; Bjursten, Lars Magnus LU and Frangos, J A (2006) In Bone 38(1). p.93-104
Abstract
In osteoblasts, cyclooxygenase 2 (COX-2) is the major isozyme responsible for production of prostaglandins. Prostaglandins are local mediators of bone resorption and formation and are known to be involved in bone's adaptive response to fluid shear stress (FSS). We have previously described a model of trabecular bone loss in hindlimb-suspended mice and rats and demonstrated partial protection from osteopenia by ligation of the femoral vein. The increased FSS resulting from this ligation drove bone adaptation in the absence of mechanical loading. In this study, we investigated the role of COX-2 in this adaptive response to FSS by use of COX-2 knockout mice. COX-2 knockout ("KO"), COX-2 heterozygote ("HET"), and COX-2 wild-type ("WT") animals... (More)
In osteoblasts, cyclooxygenase 2 (COX-2) is the major isozyme responsible for production of prostaglandins. Prostaglandins are local mediators of bone resorption and formation and are known to be involved in bone's adaptive response to fluid shear stress (FSS). We have previously described a model of trabecular bone loss in hindlimb-suspended mice and rats and demonstrated partial protection from osteopenia by ligation of the femoral vein. The increased FSS resulting from this ligation drove bone adaptation in the absence of mechanical loading. In this study, we investigated the role of COX-2 in this adaptive response to FSS by use of COX-2 knockout mice. COX-2 knockout ("KO"), COX-2 heterozygote ("HET"), and COX-2 wild-type ("WT") animals all lost comparable amounts of trabecular bone from sham-operated limbs as a result of suspension. In WT mice, loss of trabecular BMD in the venous-ligated limb was significantly less than that of the sham-operated limb; this effect, however, was not seen in KO or HET mice. Percentage gain in femoral periosteal circumference was greater in the ligated limb than the sham-operated limb for WT mice. KO and HET mice already possess femora of larger periosteal circumference than their WT littermates and ligation in these bones did not result in an increase in perimeter relative to sham. Histomorphometry on embedded bones revealed thinner cortices and less mineralizing perimeter in KO femora than controls. In conclusion, this is the first in vivo study to show that fluid-flow-mediated bone adaptation, independent of mechanical strain, is COX-2 dependent. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Interstitial fluid flow, Bone (re)modeling, Cyclooxygenase-2, Knockout mice, Hindlimb suspension
in
Bone
volume
38
issue
1
pages
93 - 104
publisher
Elsevier
external identifiers
  • pmid:16122997
  • scopus:29344455096
ISSN
1873-2763
DOI
10.1016/j.bone.2005.07.006
language
English
LU publication?
yes
id
431c3a85-35e5-40b9-a374-fac75464e589 (old id 1135333)
date added to LUP
2008-06-13 12:50:37
date last changed
2019-01-06 09:38:13
@article{431c3a85-35e5-40b9-a374-fac75464e589,
  abstract     = {In osteoblasts, cyclooxygenase 2 (COX-2) is the major isozyme responsible for production of prostaglandins. Prostaglandins are local mediators of bone resorption and formation and are known to be involved in bone's adaptive response to fluid shear stress (FSS). We have previously described a model of trabecular bone loss in hindlimb-suspended mice and rats and demonstrated partial protection from osteopenia by ligation of the femoral vein. The increased FSS resulting from this ligation drove bone adaptation in the absence of mechanical loading. In this study, we investigated the role of COX-2 in this adaptive response to FSS by use of COX-2 knockout mice. COX-2 knockout ("KO"), COX-2 heterozygote ("HET"), and COX-2 wild-type ("WT") animals all lost comparable amounts of trabecular bone from sham-operated limbs as a result of suspension. In WT mice, loss of trabecular BMD in the venous-ligated limb was significantly less than that of the sham-operated limb; this effect, however, was not seen in KO or HET mice. Percentage gain in femoral periosteal circumference was greater in the ligated limb than the sham-operated limb for WT mice. KO and HET mice already possess femora of larger periosteal circumference than their WT littermates and ligation in these bones did not result in an increase in perimeter relative to sham. Histomorphometry on embedded bones revealed thinner cortices and less mineralizing perimeter in KO femora than controls. In conclusion, this is the first in vivo study to show that fluid-flow-mediated bone adaptation, independent of mechanical strain, is COX-2 dependent.},
  author       = {Stevens, H Y and Meays, D R and Yeh, J and Bjursten, Lars Magnus and Frangos, J A},
  issn         = {1873-2763},
  keyword      = {Interstitial fluid flow,Bone (re)modeling,Cyclooxygenase-2,Knockout mice,Hindlimb suspension},
  language     = {eng},
  number       = {1},
  pages        = {93--104},
  publisher    = {Elsevier},
  series       = {Bone},
  title        = {COX-2 is necessary for venous ligation-mediated bone adaptation in mice},
  url          = {http://dx.doi.org/10.1016/j.bone.2005.07.006},
  volume       = {38},
  year         = {2006},
}