Unloading induces osteoblastic cell suppression and osteoclastic cell activation to lead to bone loss via sympathetic nervous system
Unloading induces osteoblastic cell suppression and osteoclastic cell activation to lead to bone loss via sympathetic nervous system
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DOI：
10.1074/jbc.m504179200
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发表时间：
2005-08-26
影响因子：
4.8
通讯作者：
Noda, M
中科院分区：
文献类型：
--
作者：
Kondo, H;Nifuji, A;Noda, M
骨质疏松症是我们现代世界的主要健康问题之一。特别是，废用性（卸载）骨质疏松症通常发生在卧床不起的患者中，这是一个由于衰老相关疾病而迅速增加的人群。然而，这种卸载引起的病理性骨丢失的机制尚未完全了解。由于交感神经系统可以控制骨量，我们研究了是否由交感神经张力控制卸载引起的骨丢失。用β受体阻滞剂普萘洛尔治疗，抑制了卸载引起的骨量减少。相反，β-受体激动剂异丙肾上腺素降低了负荷小鼠的骨量，并且在这种条件下，卸载不再进一步降低骨量。细胞基础的分析表明，unloadinginduced减少成骨细胞的活动水平，包括矿物沉积率，矿化表面，和骨形成率，受到普萘洛尔治疗和异丙肾上腺素诱导的减少，这些水平的骨形成参数不再抑制卸载。体内普萘洛尔治疗抑制了骨髓细胞培养物中卸载诱导的矿化结节形成水平的降低。此外，多巴胺β-羟化酶基因中一半剂量的损失抑制了卸载诱导的骨丢失和矿化结节形成的减少。卸载诱导的破骨细胞活性水平的增加，如破骨细胞的数量和表面，以及尿脱氧吡啶啉都抑制了普萘洛尔的治疗。这些观察结果表明，交感神经紧张介导的卸载诱导的骨丢失通过抑制骨形成的成骨细胞和破骨细胞的吸收增强。
Osteoporosis is one of the major health problems in our modern world. Especially, disuse ( unloading) osteoporosis occurs commonly in bedridden patients, a population that is rapidly increasing due to aging-associated diseases. However, the mechanisms underlying such unloading-induced pathological bone loss have not yet been fully understood. Since sympathetic nervous system could control bone mass, we examined whether unloading-induced bone loss is controlled by sympathetic nervous tone. Treatment with beta-blocker, propranolol, suppressed the unloading-induced reduction in bone mass. Conversely, beta-agonist, isoproterenol, reduced bone mass in loaded mice, and under such conditions, unloading no longer further reduced bone mass. Analyses on the cellular bases indicated that unloadinginduced reduction in the levels of osteoblastic cell activities, including mineral apposition rate, mineralizing surface, and bone formation rate, was suppressed by propranolol treatment and that isoproterenol-induced reduction in these levels of bone formation parameters was no longer suppressed by unloading. Unloading- induced reduction in the levels of mineralized nodule formation in bone marrow cell cultures was suppressed by propranolol treatment in vivo. In addition, loss of a half-dosage in the dopamine beta-hydroxylase gene suppressed the unloading-induced bone loss and reduction in mineralized nodule formation. Unloading-induced increase in the levels of osteoclastic activities such as osteoclast number and surface as well as urinary deoxypyridinoline was all suppressed by the treatment with propranolol. These observations indicated that sympathetic nervous tone mediates unloading-induced bone loss through suppression of bone formation by osteoblasts and enhancement of resorption by osteoclasts.