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Int. J. Mol. Sci. 2011, 12(7), 4206-4213; doi:10.3390/ijms12074206
Short Note

Reciprocal Roles of Angiotensin II and Angiotensin II Receptors Blockade (ARB) in Regulating Cbfa1/RANKL via cAMP Signaling Pathway: Possible Mechanism for Hypertension-Related Osteoporosis and Antagonistic Effect of ARB on Hypertension-Related Osteoporosis

1
, 1
 and 2,*
Received: 14 April 2011; in revised form: 20 May 2011 / Accepted: 14 June 2011 / Published: 27 June 2011
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Abstract: Hypertension is a risk factor for osteoporosis. Animal and epidemiological studies demonstrate that high blood pressure is associated with increased calcium loss, elevated parathyroid hormone, and increased calcium movement from bone. However, the mechanism responsible for hypertension-related osteoporosis remains elusive. Recent epidemiological studies indicate the benefits of Angiotensin II Receptors Blockade (ARB) on decreasing fracture risks. Since receptors for angiotensin II, the targets of ARB, are expressed in both osteoblasts and osteoclasts, we postulated that angiotensin II plays an important role in hypertension-related osteoporosis. Cbfa1 and RANKL, the important factors for maintaining bone homeostasis and key mediators in controlling osteoblast and osteoclast differentiation, are both regulated by cAMP-dependent signaling. Angiotensin II along with factors such as LDL, HDL, NO and homocysteine that are commonly altered both in hypertension and osteoporosis, can down-regulate the expression of Cbfa1 but up-regulate RANKL expression via the cAMP signaling pathway. We thus hypothesized that, by altering the ratio of Cbfa1/RANKL expression via the cAMP-dependent pathway, angiotensin II differently regulates osteoblast and osteoclast differentiation leading to enhanced bone resorption and reduced bone formation. Since ARB can antagonize the adverse effect of angiotensin II on bone by lowering cAMP levels and modifying other downstream targets, including LDL, HDL, NO and Cbfa1/RANKL, we propose the hypothesis that the antagonistic effects of ARB may also be exerted via cAMP signaling pathway.
Keywords: hypertension; osteoporosis; angiotensin II; ARB; Cbfa1; RANKL; cAMP hypertension; osteoporosis; angiotensin II; ARB; Cbfa1; RANKL; cAMP
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Guan, X.-X.; Zhou, Y.; Li, J.-Y. Reciprocal Roles of Angiotensin II and Angiotensin II Receptors Blockade (ARB) in Regulating Cbfa1/RANKL via cAMP Signaling Pathway: Possible Mechanism for Hypertension-Related Osteoporosis and Antagonistic Effect of ARB on Hypertension-Related Osteoporosis. Int. J. Mol. Sci. 2011, 12, 4206-4213.

AMA Style

Guan X-X, Zhou Y, Li J-Y. Reciprocal Roles of Angiotensin II and Angiotensin II Receptors Blockade (ARB) in Regulating Cbfa1/RANKL via cAMP Signaling Pathway: Possible Mechanism for Hypertension-Related Osteoporosis and Antagonistic Effect of ARB on Hypertension-Related Osteoporosis. International Journal of Molecular Sciences. 2011; 12(7):4206-4213.

Chicago/Turabian Style

Guan, Xiao-Xu; Zhou, Yi; Li, Ji-Yao. 2011. "Reciprocal Roles of Angiotensin II and Angiotensin II Receptors Blockade (ARB) in Regulating Cbfa1/RANKL via cAMP Signaling Pathway: Possible Mechanism for Hypertension-Related Osteoporosis and Antagonistic Effect of ARB on Hypertension-Related Osteoporosis." Int. J. Mol. Sci. 12, no. 7: 4206-4213.


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