Osteoprotegerin reduces the serum level of receptor activator of NF-κB ligand derived from osteoblasts
Osteoprotegerin reduces the serum level of receptor activator of NF-κB ligand derived from osteoblasts
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DOI：
10.4049/jimmunol.178.1.192
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Takahashi, Naoyuki
中科院分区：
文献类型：
--
作者：
Nakamichi, Yuko;Udagawa, Nobuyuki;Takahashi, Naoyuki
骨保护素（OPG）是NF-κ B配体受体激活剂（RANKL）的诱饵受体。我们以前报道过OPG缺乏会升高小鼠RANKL的循环水平。使用OPG（-/-）小鼠，我们研究了OPG是否参与表达RANKL的细胞对RANKL的脱落。培养的成骨细胞和活化的T细胞在不存在OPG的情况下释放大量的RANKL。OPG或NF-κ B（RANKL的受体）受体激活剂的可溶性形式抑制RANKL从这些细胞中的释放。OPG和T细胞双缺陷小鼠显示血清RANKL水平升高，与OPG（-/-）小鼠相当，表明循环RANKL主要来源于骨。OPG（-/-）小鼠中RANKL的血清水平通过卵巢切除术或给予1 α，25-二羟维生素D-3而升高。在野生型和OPG（-/-）小鼠中，1a，25-二羟维生素D，增加了骨中RANKL mRNA的表达，但未增加胸腺或脾脏中RANKL mRNA的表达。这些结果表明，OPG抑制RANKL从成骨细胞脱落，OPG（-/-）小鼠血清RANKL准确反映了骨吸收的状态。
Osteoprotegerin (OPG) is a decoy receptor for receptor activator of NF-kappa B ligand (RANKL). We previously reported that OPG deficiency elevated the circulating level of RANKL in mice. Using OPG(-/-) mice, we investigated whether OPG is involved in the shedding of RANKL by cells expressing RANKL. Osteoblasts and activated T cells in culture released a large amount of RANKL in the absence of OPG. OPG or a soluble form of receptor activator of NF-kappa B (the receptor of RANKL) suppressed the release of RANKL from those cells. OPG- and T cell-double-deficient mice showed an elevated serum RANKL level equivalent to that of OPG(-/-) mice, indicating that circulating RANKL is mainly derived from bone. The serum level of RANKL in OPG(-/-) mice was increased by ovariectomy or administration of 1 alpha,25-dihydroxyvitamin D-3. Expression of RANKL mRNA in bone, but not thymus or spleen, was increased in wild-type and OPG(-/-) mice by la,25-dihydroxyvitamin D,. These results suggest that OPG suppresses the shedding of RANKL from osteoblasts and that the serum RANKL in OPG(-/-) mice exactly reflects the state of bone resorption.