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[激素与骨质疏松症的最新进展。血管紧张素II对骨代谢的影响]

[Hormones and osteoporosis update. Effect of angiotensin II on bone metabolism].

作者信息

Nakagami Hironori, Morishita Ryuichi

机构信息

Division of Geno Therapy Science, Osaka University.

出版信息

Clin Calcium. 2009 Jul;19(7):997-1002.

Abstract

Bone metabolism is closely regulated by hormones and cytokines, which have effects on both bone resorption and deposition. Since renin-angiotensin system (RAS) has been known to play an important role to regulate remodeling in several tissues, we focused on the potential role of RAS in bone metabolism. It is known that the receptors of angiotensin II are expressed in culture osteoclasts and osteoblasts, and angiotensin II induced the differentiation and activation of osteoclasts responsible for bone resorption. Of importance, angiotensin II significantly induced the expression of RANKL (receptor activator of NF-kappaB ligand) in osteoblasts, leading to the activation of osteoclasts, while these effects were completely blocked by an angiotensin II type 1 receptor blockade. In a rat ovariectomy model of estrogen deficiency, administration of angiotensin II accelerated the increase in TRAP activity, accompanied by a significant decrease in bone density and an increase in urinary deoxypyridinoline. As it has been known that osteoclast differentiation is regulated by a variety of hormones, local factors and inflammatory cytokines, such as IL-1 and TNF-alpha, RAS might also be involved in this autocrine system. Of importance, sub-analysis of recent clinical study demonstrated that the usage of angiotensin-converting enzyme inhibitors significantly reduced the fracture risk. RAS might be a novel target to treat the subgroups of hypertensive patients with osteoporosis.

摘要

骨代谢受到激素和细胞因子的密切调控,这些激素和细胞因子对骨吸收和骨沉积均有影响。由于已知肾素-血管紧张素系统(RAS)在多种组织的重塑调节中发挥重要作用,我们重点研究了RAS在骨代谢中的潜在作用。已知血管紧张素II的受体在培养的破骨细胞和成骨细胞中表达,并且血管紧张素II可诱导负责骨吸收的破骨细胞的分化和激活。重要的是,血管紧张素II可显著诱导成骨细胞中RANKL(核因子κB受体激活剂配体)的表达,从而导致破骨细胞的激活,而这些作用可被血管紧张素II 1型受体阻滞剂完全阻断。在雌激素缺乏的大鼠卵巢切除模型中,给予血管紧张素II可加速抗酒石酸酸性磷酸酶(TRAP)活性的增加,同时伴有骨密度显著降低和尿脱氧吡啶啉增加。由于已知破骨细胞的分化受多种激素、局部因子和炎性细胞因子(如白细胞介素-1和肿瘤坏死因子-α)的调节,RAS可能也参与了这一自分泌系统。重要的是,近期一项临床研究的亚组分析表明,使用血管紧张素转换酶抑制剂可显著降低骨折风险。RAS可能是治疗患有骨质疏松症的高血压患者亚组的一个新靶点。

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