COX-2 is necessary for venous ligation-mediated bone adaptation in mice.
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.
Stevens
H Y
HY
La Jolla Bioengineering Institute, 505 Coast Boulevard South, La Jolla, CA 92037, USA.
Meays
D R
DR
Yeh
J
J
Bjursten
L M
LM
Frangos
J A
JA
D000818:Animals; D015519:Bone Density / Q000235:genetics; D016723:Bone Remodeling / Q000235:genetics*; D003433:Crosses, Genetic; D051546:Cyclooxygenase 2 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D005260:Female; D005268:Femoral Vein / Q000201:enzymology*; D006579:Heterozygote; D006614:Hindlimb; D008026:Ligation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D013686:Telemetry; D014057:Tomography, X-Ray Computed
D051546:Cyclooxygenase 2