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Angiotensin II accelerates osteoporosis by activating osteoclasts
Author(s) -
Shimizu Hideo,
Nakagami Hironori,
Osako Mariana Kiomy,
Hanayama Rie,
Kunugiza Yasuo,
Kizawa Takuji,
Tomita Tetsuya,
Yoshikawa Hideki,
Ogihara Toshio,
Morishita Ryuichi
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-098954
Subject(s) - medicine , endocrinology , rankl , deoxypyridinoline , bone remodeling , chemistry , bone resorption , osteoporosis , angiotensin ii , losartan , osteoclast , renin–angiotensin system , receptor , activator (genetics) , osteocalcin , alkaline phosphatase , enzyme , blood pressure , biochemistry
Recent clinical studies suggest that several antihypertensive drugs, especially angiotensin‐converting enzyme inhibitors, reduced bone fractures. To clarify the relationship between hypertension and osteoporosis, we focused on the role of angiotensin II (Ang II) on bone metabolism. In bone marrow‐derived mononuclear cells, Ang II (1×10 −6 M) significantly increased tartrate‐resistant acid phosphatase (TRAP) ‐positive multinuclear osteoclasts. Of importance, Ang II significantly induced the expression of receptor activator of nf‐κb ligand (RANKL) in osteoblasts, leading to the activation of osteoclasts, whereas these effects were completely blocked by an Ang II type 1 receptor blockade (olmesartan) and mitogen‐activated protein kinase kinase inhibitors. In a rat ovariectomy model of estrogen deficiency, administration of Ang II (200 ng/kg/min) accelerated the increase in TRAP activity, accompanied by a significant decrease in bone density and an increase in urinary deoxypyridinoline. In hypertensive rats, treatment with olmesartan attenuated the ovariectomy‐induced decrease in bone density and increase in TRAP activity and urinary deoxypyridinoline. Furthermore, in wild‐type mice ovariectomy with five‐sixths nephrectomy decreased bone volume by microcomputed tomography, whereas these change was not detect in Ang II type 1a receptor‐deficient mice. Overall, Ang II accelerates osteoporosis by activating osteoclasts via RANKL induction. Blockade of Ang II might become a novel therapeutic approach to prevent osteoporosis in hypertensive patients.—Shimizu, H., Nakagami, H., Osako, M. K., Hanayama, R., Kunugiza, Y., Kizawa, T., Tomita, T., Yoshikawa, H., Ogihara, T., Morishita, R. Angiotensin II accelerates osteoporosis by activating osteoclasts. FASEB J. 22, 2465–2475 (2008)