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.
Highlights
Osteoporosis is a common disorder that leads to reduction in bone mass, deterioration in bone microarchitecture, susceptibility to skeletal fragility, and increased risk of fracture [1]
Sci. 2011, 12 downstream targets, including low density lipoprotein (LDL), high density lipoprotein (HDL), nitric oxide (NO) and Cbfa1/RANKL, we propose the hypothesis that the antagonistic effects of Angiotensin II Receptors Blockade (ARB) may be exerted via cAMP
The differentiation of osteoblast and osteoclasts is primarily controlled by two key mediators, Cbfa1 and RANKL, which are regulated by the second messenger, cAMP [13,14,15]. It has been demonstrated by several studies that pathological conditions, including abnormal lipid metabolism, altered levels of low density lipoprotein (LDL), high density lipoprotein (HDL), plasma homocysteine and nitric oxide (NO), are involved both in hypertension and osteoporosis [16,17,18,19,20]
Summary
Osteoporosis is a common disorder that leads to reduction in bone mass, deterioration in bone microarchitecture, susceptibility to skeletal fragility, and increased risk of fracture [1]. 2. Angiotensin II Regulates Cbfa1/RANKL via the cAMP Signaling Pathway: The Possible It has been demonstrated by several studies that pathological conditions, including abnormal lipid metabolism, altered levels of low density lipoprotein (LDL), high density lipoprotein (HDL), plasma homocysteine and nitric oxide (NO), are involved both in hypertension and osteoporosis [16,17,18,19,20].
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