Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: Increased serum concentrations in postmenopausal women with osteoporosis
Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: Increased serum concentrations in postmenopausal women with osteoporosis
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DOI：
10.1359/jbmr.1999.14.4.518
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发表时间：
1999-04-01
影响因子：
6.2
通讯作者：
Yamada, Y
中科院分区：
文献类型：
--
作者：
Yano, K;Tsuda, E;Yamada, Y
骨保护素（OPG）/破骨细胞生成抑制因子（OCIF）是肿瘤坏死因子受体家族的可溶性成员，在骨吸收的负调节中起重要作用。OPG/OCIF是否在人体血液中循环以及在病理条件下其水平如何变化尚不清楚。为了解决这些问题，针对重组OPG/OCIF产生一组单克隆抗体，并筛选与重组蛋白的固相单体和同源二聚体形式的反应性。鉴定出对两种形式的OPG/OCIF均表现出高亲和力的抗体以及选择性识别同二聚体的抗体，从而开发出两种类型的敏感酶联免疫吸附测定（ELISA）：一种同等检测两种形式的OPG/OCIF，另一种对同二聚体具有特异性。用这些ELISA对循环OPG/OCIF进行表征表明，该蛋白主要以单体形式存在于人血清中。在日本健康男性和正常人中，血清OPG/OCIF浓度均随年龄增长而增加，绝经后骨质疏松症女性的血清OPG/OCIF浓度显著高于年龄匹配的对照组。通过测定血清骨特异性碱性磷酸酶和尿吡啶啉和脱氧吡啶啉排泄量，发现骨转换率高的绝经后妇女血清OPG/OCIF浓度也显著升高。结果表明，循环OPG/OCIF水平受年龄相关因素的调节，血清浓度升高可能反映了对骨吸收增强的代偿反应和由此导致的骨丢失，而不是骨质疏松症的原因。
Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a soluble member of the tumor necrosis factor receptor family of proteins and plays an important role in the negative regulation of osteoclastic hone resorption, Whether OPG/OCIF circulates in human blood and how its level changes under pathological conditions is not known. To address these issues, a panel of monoclonal antibodies was generated against recombinant OPG/OCIF and screened for reactivity with solid-phase monomeric and homodimeric forms of the recombinant protein. Antibodies that showed high affinity for both forms of OPG/OCIF and those that selectively recognized the homodimer were identified, enabling development of two types of sensitive enzyme-linked immunosorbent assay (ELISA): one that detects both forms of OPG/OCIF equally and one specific for the homodimer. Characterization of circulating OPG/OCIF with these ELISAs revealed that the protein exists in human serum mainly in the monomeric form. The serum concentration of OPG/OCIF increased with age in both healthy Japanese men and nomen, and was significantly higher in postmenopausal women with osteoporosis than in age-matched controls, Within the osteoporotic group, serum OPG/OCIF concentrations were higher in patients with low bone mass. Serum OPG/OCIF concentrations were also significantly increased in those postmenopausal women with a high rate of bone turnover, as determined by increased serum bone-specific alkaline phosphatase and urinary excretion of pyridinoline and deoxypyridinoline. The results suggested that circulating OPG/OCIF levels are regulated by an age-related factor(s) and that the increased serum concentration may reflect a compensative response to enhanced osteoclastic bone resorption and the resultant bone loss rather than a cause of osteoporosis.