The isozyme-specific effects of cyclooxygenase-deficiency on bone in mice.
Prostaglandin E(2) (PGE(2)) plays a critical role in skeletal physiology and bone loss. PGE(2) production is regulated in vivo by at least two cyclooxygenase (COX) isozymes, COX-1 and COX-2. The purpose of this study was to investigate the in vivo effects of the selective deletion of COX-1 or COX-2 on bone mineral density (BMD), bone microarchitecture and bone strength in wild type (WT), COX-1(-/-) and COX-2(-/-) mice. Using a LUNAR PIXImus, BMD was measured in 18 (WT), 18 COX-1(-/-) and 16 COX-2(-/-) mice. COX-1(-/-) mice exhibited significantly higher BMD (0.0506 g/cm(2) +/- 0.0014 g/cm(2)) than either WT (0.0493 g/cm(2) +/- 0.0019, P < or = 0.05) or COX-2(-/-) (0.0473 g/cm(2) +/- 0.0034, P < or = 0.01) mice. COX-2(-/-) mice had significantly lower BMD than WT (P < or = 0.01) or COX-1(-/-) (P < or = 0.01). Flexure stress of the femurs, determined by breaking the bones with three-point bending, correlated with bone density. Although plasma levels of both Ca(2+) and PTH were comparable in wild type and COX-1(-/-) mice, both were elevated in COX-2(-/-) mice consistent with primary hyperparathyroidism. These studies suggest that COX enzymes are important regulators of BMD and bone strength in mice. The beneficial effect of absence of the COX-1 enzyme on skeletal parameters may be secondary to decreases in PGE(2). On the other hand, primary hyperparathyroidism and lower bone magnesium content may account for the lower BMD and impairments in bone strength of COX-2(-/-) mice. Further elucidation of the effects of the COX pathway on bone remodeling may provide important information on potential therapeutic targets for preventing and/or treating osteoporosis.
Myers
L K
LK
University of Tennessee Health Science Center, College of Medicine, 956 Court Avenue, Room G326, University of Tennessee, Memphis, TN 38163, USA. Electronic address: lmyers@utmem.edu.
Bhattacharya
S D
SD
University of Tennessee Health Science Center, College of Medicine, 956 Court Avenue, Room G326, University of Tennessee, Memphis, TN 38163, USA.
Herring
P A
PA
University of Tennessee Health Science Center, College of Medicine, 956 Court Avenue, Room G326, University of Tennessee, Memphis, TN 38163, USA.
Xing
Z
Z
University of Tennessee Health Science Center, College of Medicine, 956 Court Avenue, Room G326, University of Tennessee, Memphis, TN 38163, USA.
Goorha
S
S
Research Service of the Veterans Affairs Medical Center, Memphis, TN, USA.
Smith
R A
RA
University of Tennessee Health Science Center, College of Medicine, 956 Court Avenue, Room G326, University of Tennessee, Memphis, TN 38163, USA.
Bhattacharya
S K
SK
University of Tennessee Health Science Center, College of Medicine, 956 Court Avenue, Room G326, University of Tennessee, Memphis, TN 38163, USA.
Carbone
L
L
University of Tennessee Health Science Center, College of Medicine, 956 Court Avenue, Room G326, University of Tennessee, Memphis, TN 38163, USA.
Faccio
Roberta
R
Department of Orthopaedic Surgery, Washington University, St. Louis, MO, USA.
Kang
A H
AH
University of Tennessee Health Science Center, College of Medicine, 956 Court Avenue, Room G326, University of Tennessee, Memphis, TN 38163, USA; Research Service of the Veterans Affairs Medical Center, Memphis, TN, USA.
Ballou
L R
LR
University of Tennessee Health Science Center, College of Medicine, 956 Court Avenue, Room G326, University of Tennessee, Memphis, TN 38163, USA; Research Service of the Veterans Affairs Medical Center, Memphis, TN, USA; University of Tennessee Health Science Center, Department of Molecular Sciences, Memphis, TN, USA.
D000818:Animals; D001696:Biomechanical Phenomena; D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000097:blood; D051545:Cyclooxygenase 1 / Q000172:deficiency* / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000172:deficiency* / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005269:Femur / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D010281:Parathyroid Hormone / Q000097:blood
D010281:Parathyroid Hormone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D002118:Calcium