Osteopontin deficiency suppresses high phosphate load-induced bone loss via specific modulation of osteoclasts
Osteopontin deficiency suppresses high phosphate load-induced bone loss via specific modulation of osteoclasts
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DOI：
10.1210/en.2005-0671
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发表时间：
2006-06-01
期刊：
影响因子：
4.8
通讯作者：
Noda, Masaki
中科院分区：
文献类型：
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作者：
Koyama, Yuki;Rittling, Susan R.;Noda, Masaki
磷酸盐（Pi）在维持矿化组织和细胞内环境中的信号传导中起着关键作用。虽然细胞外磷酸盐浓度维持在固定水平，但骨中磷酸盐稳态的生理机制尚未完全阐明，骨是最大的磷酸盐储存部位。在这里，我们研究了骨桥蛋白（OPN）在高磷饮食负荷诱导的骨丢失中的作用。高磷饮食显着降低骨密度以及野生型骨量。相反，OPN缺乏完全阻止了骨密度和骨量的降低。骨转换相关成分的分析表明，骨形成参数（骨形成率和矿物质沉积率）增强高磷饮食负荷类似于野生型和OPN缺陷小鼠。与此形成鲜明对比的是，骨吸收参数（破骨细胞数量和破骨细胞表面）增强高磷饮食负荷在野生型，但不是在所有的OPN缺陷型小鼠。骨髓细胞培养显示OPN缺乏对培养物中矿化结节形成的高Pi饮食调节没有重大影响。另一方面，抗酒石酸酸性磷酸酶阳性的多核细胞的发展，在文化中的野生型细胞的高Pi饮食负荷增强，但这种影响的高Pi饮食的情况下，OPN完全取消。这些数据表明，骨桥蛋白是骨细胞活性所必需的，以在高磷酸盐负荷下吸收骨。
Phosphate (Pi) plays a critical role in the maintenance of mineralized tissues and signaling in the intracellular environment. Although extracellular phosphate concentration is maintained at fixed levels, physiological machineries involved in phosphate homeostasis in bone, which is the largest phosphate storage site, have not yet been fully elucidated. Here we examined the role of osteopontin (OPN) in a high-Pi diet load-induced bone loss. A high-Pi diet significantly reduced bone mineral density as well as bone mass in wild type. In contrast, OPN deficiency totally prevented reduction in bone mineral density and bone mass. Analyses of bone turnover-related components revealed that bone formation parameters (bone formation rate and mineral apposition rate) were enhanced by high-Pi diet load similarly in wild-type and OPN-deficient mice. In sharp contrast, bone resorption parameters (osteoclast number and osteoclast surface) were enhanced by high-Pi diet load in wild type but not at all in OPN-deficient mice. Bone marrow cell cultures revealed no major effects of OPN deficiency on high-Pi diet modulation of mineralized nodule formation in culture. On the other hand, tartrate-resistant acid phosphatase-positive multinucleated cell development in cultures were enhanced by high-Pi diet load in wild-type cells, but such effects of high Pi-diet were totally abolished in the absence of OPN. These data indicated that OPN is needed for osteoclastic activity to resorb bone on high phosphate loading.