Bone re/modeling is more dynamic in the endothelial nitric oxide synthase(-/-) mouse.
Nitric oxide is a ubiquitous estrogen-regulated signaling molecule that has been implicated in the regulation of bone maturation and remodeling. To better understand the role that bone-cell-secreted nitric oxide plays in ovariectomy-induced modifications of bone turnover, we examined the expression of endothelial NO synthase (eNOS) in bone cells and bone progenitor cells at regular intervals up to 10 wk after acute estrogen deprivation. Ovariectomy led to an anticipated initial decline in bone cell eNOS production, but surprisingly, 17 d after ovariectomy, eNOS expression by bone and marrow stromal cells dramatically rebounded and was maintained at high levels for at least 10 wk after surgery. We examined the long-term consequences of eNOS in the process of ovariectomy-induced bone loss by prospectively analyzing bone mineral density in wild-type and eNOS(-/-) mice for 10 wk after ovariectomy. Ovariectomized eNOS(-/-) mice were observed to undergo an exaggerated state of estrogen-deficiency-induced bone remodeling compared with wild-type controls, suggesting that eNOS may act to mitigate this process. Furthermore, we found that whereas bone formation in estrogen-replete wild-type mice slowed between 14 and 20 wk of age, eNOS knockout mice continued to accrue basal bone mass at a high rate and showed no sign of entering a remodeling stage. Our data suggest that eNOS may play an important role in limiting ovariectomy-induced bone remodeling as well as regulating the transition from basal modeling to remodeling.
Grassi
F
F
Division of Endocrinology, Metabolism and Lipids, Emory University, Atlanta, Georgia 30332, USA.
Fan
X
X
Rahnert
J
J
Weitzmann
M N
MN
Pacifici
R
R
Nanes
M S
MS
Rubin
J
J
D000818:Animals; D015519:Bone Density; D001854:Bone Marrow Cells / Q000201:enzymology; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000378:metabolism; D002478:Cells, Cultured; D004967:Estrogens / Q000172:deficiency / Q000502:physiology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D010052:Ovariectomy; D013997:Time Factors; D014057:Tomography, X-Ray Computed
D004967:Estrogens; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III