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Angiotensin II accelerates osteoporosis by activating osteoclasts
Hideo Shimizu1, Hironori Nakagami, Mariana Kiomy Osako
1Division of Clinical Gene Therapy, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Summary
Angiotensin II (Ang II) accelerates osteoporosis by increasing osteoclast activity via RANKL induction. Blocking Ang II may offer a new strategy for preventing bone loss in hypertensive individuals.
Area of Science:
- Bone Metabolism
- Endocrinology
- Pharmacology
Background:
- Clinical studies indicate antihypertensive drugs may reduce bone fractures.
- The precise relationship between hypertension and osteoporosis requires further elucidation.
- Angiotensin II (Ang II) is investigated for its potential role in bone metabolism.
Purpose of the Study:
- To clarify the relationship between hypertension and osteoporosis.
- To investigate the role of Ang II in bone metabolism.
- To determine the therapeutic potential of Ang II blockade in preventing osteoporosis.
Main Methods:
- Assessed Ang II effects on osteoclast formation and RANKL expression in vitro.
- Utilized a rat ovariectomy model to study Ang II in estrogen-deficient osteoporosis.
- Administered Ang II and olmesartan in rat and mouse models of bone loss.
- Employed microcomputed tomography to evaluate bone density changes.
Main Results:
- Ang II significantly increased osteoclast activity and RANKL expression in vitro.
- Ang II administration accelerated bone density loss and increased bone resorption markers in ovariectomized rats.
- Olmesartan treatment attenuated Ang II-induced bone loss and resorption.
- Ang II type 1a receptor deficiency protected against ovariectomy-induced bone volume reduction in mice.
Conclusions:
- Angiotensin II accelerates osteoporosis by promoting osteoclast activation through RANKL induction.
- Blockade of the Ang II pathway, specifically via Ang II type 1 receptor antagonism, demonstrates potential in preventing osteoporosis.
- Targeting Ang II may represent a novel therapeutic approach for osteoporosis in hypertensive patients.
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