A chimeric form of osteoprotegerin inhibits hypercalcemia and bone resorption induced by IL-1β, TNF-α, PTH, PTHrP, and 1,25(OH)2D3
A chimeric form of osteoprotegerin inhibits hypercalcemia and bone resorption induced by IL-1β, TNF-α, PTH, PTHrP, and 1,25(OH)2D3
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DOI：
10.1359/jbmr.1999.14.9.1478
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发表时间：
1999-09-01
影响因子：
6.2
通讯作者：
Dunstan, CR
中科院分区：
文献类型：
--
作者：
Morony, S;Capparelli, C;Dunstan, CR
骨保护素(OPG)是一种分泌蛋白，可抑制破骨细胞的形成和活性，是骨量和代谢的重要调节因子。在目前的研究中，小鼠接受了各种细胞因子和激素(白介素1β、肿瘤坏死因子α、甲状旁腺激素、甲状旁腺激素相关蛋白和1α，25-二羟基维生素D-3)的刺激，这些细胞因子和激素被认为会增加骨吸收和引起高钙血症，并同时接受具有增强生物活性的重组人OPG融合形式(COPG)(2.5 mg/kg/天)或赋形剂治疗，接受这些骨吸收因子的小鼠在开始治疗后的第3天变得高钙血症，并增加了骨吸收，如第5天破骨细胞数量增加所证明的，同时cOPG治疗预防了高钙血症(p<；，并将破骨细胞数量维持在正常范围内(p<；0.001)，证明cOPG可以抑制骨吸收，这表明该分子可能用于治疗包括甲状旁腺功能亢进症、恶性肿瘤体液高钙血症、骨质疏松症和炎症性骨病等疾病，这些疾病的部分特征是破骨细胞性骨吸收增加。
Osteoprotegerin (OPG) is a secreted protein that inhibits osteoclast formation and activity and appears to be a critical regulator of bone mass and metabolism. In the current study, mice were challenged with various cytokines and hormones (interleukin-1 beta, tumor necrosis factor-alpha, parathyroid hormone, parathyroid hormone-related protein, and 1 alpha,25-dihydroxyvitamin D-3) that are known to increase bone resorption and cause hypercalcemia and treated concurrently with either a recombinant chimeric Fc fusion form of human OPG, with enhanced biological activity (cOPG) (2.5 mg/kg/day) or vehicle, Mice receiving these bone-resorbing factors became hypercalcemic by day 3 after commencing treatment and had increased bone resorption as evidenced by elevated osteoclast numbers on day 5, Concurrent cOPG treatment prevented hypercalcemia (p < 0.05) and maintained osteoclast numbers in the normal range(p < 0.001), The demonstration that cOPG can inhibit bone resorption suggests that this molecule may be useful in the treatment of diseases including hyperparathyroidism, humoral hypercalcemia of malignancy, osteoporosis, and inflammatory bone disease, which are characterized, in part, by increases in osteoclastic bone resorption.