Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin.
Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin.
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DOI：
10.1084/jem.193.3.399
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发表时间：
2001-02-05
期刊：
影响因子：
--
通讯作者：
Noda M
中科院分区：
文献类型：
--
作者：
Ishijima M;Rittling SR;Yamashita T;Tsuji K;Kurosawa H;Nifuji A;Denhardt DT;Noda M
卧床不起的患者和宇航员的骨骼机械应力降低导致骨丢失和骨折风险增加，这是现代老龄化社会和航天医学的主要医疗和健康问题之一。然而，迄今为止还没有发现这种现象背后的机制中涉及的分子。骨桥蛋白（OPN）是骨基质中主要的非胶原蛋白之一，但其在体内介导物理力作用于骨的功能尚不清楚。为了研究体内骨代谢中机械信号转导对OPN的可能需求，我们使用尾部悬吊模型检查了OPN−/−小鼠骨骼的卸载效应。与野生型小鼠尾部悬吊诱导的骨丢失相反，OPN−/−小鼠没有骨丢失。在野生型小鼠中观察到由于卸载导致的尿脱氧吡啶啉水平升高，但在OPN−/−小鼠中未观察到。在细胞基础上分析骨中OPN缺乏依赖性减少的机制导致两个意外的发现。首先，野生型小鼠中的破骨细胞因卸载而增加，而OPN-/-小鼠中的尾部悬挂并没有增加破骨细胞。第二，成骨细胞骨形成的测量，在野生型小鼠中由于卸载而减少，在OPN−/−小鼠中没有改变。这些观察结果表明，OPN的存在是活化骨细胞骨吸收和减少成骨细胞骨形成的先决条件。因此，OPN是机械应力诱导的骨丢失所需的分子，其调节成骨细胞和破骨细胞的功能。
Reduced mechanical stress to bone in bedridden patients and astronauts leads to bone loss and increase in fracture risk which is one of the major medical and health issues in modern aging society and space medicine. However, no molecule involved in the mechanisms underlying this phenomenon has been identified to date. Osteopontin (OPN) is one of the major noncollagenous proteins in bone matrix, but its function in mediating physical-force effects on bone in vivo has not been known. To investigate the possible requirement for OPN in the transduction of mechanical signaling in bone metabolism in vivo, we examined the effect of unloading on the bones of OPN−/− mice using a tail suspension model. In contrast to the tail suspension–induced bone loss in wild-type mice, OPN−/− mice did not lose bone. Elevation of urinary deoxypyridinoline levels due to unloading was observed in wild-type but not in OPN−/− mice. Analysis of the mechanisms of OPN deficiency–dependent reduction in bone on the cellular basis resulted in two unexpected findings. First, osteoclasts, which were increased by unloading in wild-type mice, were not increased by tail suspension in OPN−/− mice. Second, measures of osteoblastic bone formation, which were decreased in wild-type mice by unloading, were not altered in OPN−/− mice. These observations indicate that the presence of OPN is a prerequisite for the activation of osteoclastic bone resorption and for the reduction in osteoblastic bone formation in unloaded mice. Thus, OPN is a molecule required for the bone loss induced by mechanical stress that regulates the functions of osteoblasts and osteoclasts.
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影响因子：
6.2
作者：
Terai, K;Takano-Yamamoto, T;Nomura, S
通讯作者：
Nomura, S
影响因子：
4.8
作者：
HRUSKA, KA;ROLNICK, F;CHERESH, D
通讯作者：
CHERESH, D
影响因子：
15.9
作者：
LIAW, L;SKINNER, MP;GIACHELLI, CM
通讯作者：
GIACHELLI, CM
影响因子：
3
作者：
KUBOTA, T;YAMAUCHI, M;SODEK, J
通讯作者：
SODEK, J
影响因子：
4
作者：
Boskey, AL
通讯作者：
Boskey, AL