Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption
Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption
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DOI：
10.1210/en.2003-0717
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发表时间：
2003-12-01
期刊：
影响因子：
4.8
通讯作者：
Takahashi, N
中科院分区：
文献类型：
--
作者：
Nakamura, M;Udagawa, N;Takahashi, N
护骨素(OPG)是核因子-kappaB受体激活剂配体(RANKL)的可溶性诱饵受体，其缺乏不仅可导致骨吸收增强所致的骨质疏松，还可促进骨形成。我们使用骨吸收抑制剂利塞膦酸盐，研究了OPG(-/-)缺陷(OPG(-/-))小鼠的骨形成是否与骨吸收有关。组织形态计量学分析显示，每日注射利塞膦酸盐30d，OPG(-/-)小鼠的骨形成相关参数(如矿物质沉积率和成骨细胞表面/骨表面)急剧下降，骨吸收受到抑制，OPG(-/-)小鼠血清碱性磷酸酶活性和骨钙素浓度较高，而注射利塞膦酸盐后两者均降至野生型小鼠水平。OPG(-/-)小鼠血清RANKL水平显著升高，但利塞磷酸钠对其无明显影响。骨形态发生蛋白-2植入OPG(-/-)小鼠体内后，即使骨转换率较高，异位骨形成也不明显，但异位骨密度的降低较野生型小鼠更为明显。这些结果表明，在OPG(-/-)小鼠中，骨形成与局部部位的骨吸收是耦合的，而血清RANKL水平并不反映这种耦合。
Deficiency of osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor-kappaB ligand (RANKL), in mice induces osteoporosis caused by enhanced bone resorption, but also accelerates bone formation. We examined whether bone formation is coupled with bone resorption in OPG-deficient (OPG(-/-)) mice using risedronate, an inhibitor of bone resorption. Histomorphometric analysis showed that bone formation-related parameters (e.g. mineral apposition rate and osteoblast surface/bone surface) in OPG(-/-) mice sharply decreased with suppression of bone resorption by daily injection of risedronate for 30 d. OPG(-/-) mice exhibited high serum alkaline phosphatase activity and osteocalcin concentration, both of which were decreased to the levels in wildtype mice by the risedronate injection. Serum levels of RANKL were markedly elevated in OPG(-/-) mice, but were unaffected by risedronate. The ectopic bone formation induced by bone morphogenetic protein-2 implantation into OPG(-/-) mice was not accelerated even with a high turnover rate of bone, but attenuation of mineral density from the ectopic bone was more pronounced than that in wild-type mice. These results suggest that bone formation is coupled with bone resorption at local sites in OPG(-/-) mice, and that serum RANKL levels do not reflect this coupling.