共 39 条
Activation of Renin-Angiotensin System Induces Osteoporosis Independently of Hypertension
被引:118
作者:
Asaba, Yutaro
[1
,2
]
Ito, Masako
[3
]
Fumoto, Toshio
[1
]
Watanabe, Ken
[1
]
Flikuhara, Rvoji
[1
]
Takeshita, Sunao
[1
]
Nimura, Yuji
[2
]
Ishida, Junji
[4
]
Fukamizu, Akiyoshi
[4
,5
]
Ikeda, Kyoji
[1
]
机构:
[1] Natl Ctr Geriatr & Gerontol, Dept Bone & Joint Dis, Res Inst, Aichi 4748522, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Surg, Nagoya, Aichi 4648601, Japan
[3] Nagasaki Univ, Sch Med, Dept Radiol, Nagasaki 852, Japan
[4] Univ Tsukuba, Grad Sch Life & Environm Sci, Tsukuba, Ibaraki 305, Japan
[5] Univ Tsukuba, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki 305, Japan
关键词:
osteoporosis;
hypertension;
renin-angiotensin system;
bone resorption;
osteoclast;
BONE-MINERAL DENSITY;
BLOOD-PRESSURE;
OSTEOBLASTIC CELLS;
CONVERTING ENZYME;
AT(2) RECEPTOR;
FRACTURE RISK;
IN-VITRO;
MICE;
STROKE;
WOMEN;
D O I:
10.1359/JBMR.081006
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Hypertension and osteoporosis are two major age-related disorders however, the underlying molecular mechanism for this comorbidity is not known. The renin-angiotensin system (RAS) plays a central role in the control of blood pressure and has been all important target of antihypertensive drugs. Using a chimeric RAS model of transgenic THM (Tsukuba hypertensive mouse) expressing both the human renin and human angiotensinogen genes, we showed in this study that activation of RAS induces high turnover osteoporosis with accelerated bone resorption. Transgenic mice that express only the human renin gene were normotensive and yet exhibited a low bone mass, suggesting that osteoporosis occurs independently of the development of hypertension per se. Ex vivo cultures showed that angiotensin II (AngII) acted on osteoblasts and not directly on osteoclast precursor cells and increased osteoclastogenesis-supporting cytokines, RANKL and vascular endothelial growth factor (VEGF), thereby stimulating the formation of osteoclasts. Knockdown of AT2 receptor inhibited the AngII activity, whereas silencing of the AT1 receptor paradoxically enhanced it, suggesting a functional interaction between the two AngII receptors on the osteoblastic cell surface. Finally, treatment of THM mice with an ACE inhibitor, enalapril, improved osteoporosis and hypertension, whereas treatment with losartan, an angiotensin receptor blockers specific for AT1, resulted in exacerbation of the low bone mass phenotype. Thus, blocking the synthesis of AngII may be an effective treatment of osteoporosis and hypertension. especially for those afflicted with both conditions.
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页码:241 / 250
页数:10
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