Bone affinity of a bisphosphonate-conjugated protein in vivo
Bone affinity of a bisphosphonate-conjugated protein in vivo
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DOI：
10.1021/bp000066y
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发表时间：
2000-11-01
影响因子：
2.9
通讯作者：
Zernicke, RF
中科院分区：
文献类型：
--
作者：
Uludag, H;Gao, TJ;Zernicke, RF
能够刺激骨形成的生长因子是治疗骨质疏松症的潜在药物。然而，至关重要的是，将靶向机制纳入生长因子中，使其沉积在骨组织中，并尽量减少骨骼外部位的分布。为此，研究人员开发了一种策略，将寻骨分子1-氨基- 1,1 -二膦酸盐甲烷（aminoBP）化学偶联到模型蛋白牛血清白蛋白（BSA）上。本研究是在胫骨注射模型中评估结合物的骨亲和性。在去卵巢（OVX）大鼠实验中，BSA和氨基obp -BSA在注入胫骨髓腔后的初始（3小时）滞留量相等。1天后，在正常和OVX大鼠中，由于氨基obp偶联，获得了8倍和12倍的胫骨蛋白保留。OVX大鼠在3天后也获得了类似的结果（类似于12倍的差异）。我们得出结论，在正常和OVX大鼠中，氨基obp与BSA结合赋予了高骨亲和力和增强的骨保留蛋白。
Growth factors capable of stimulating bone formation are potential therapeutic agents for osteoporosis treatment. It is essential, however, that a targeting mechanism is incorporated into the growth factors to deposit them at osseous tissue with minimal distribution to extraskeletal sites. To this end, a strategy has been developed in which a bone-seeking molecule, 1-amino-1, 1-diphosphonate methane (aminoBP), was chemically conjugated to a model protein, bovine serum albumin (BSA). This study was carried out to assess the bone affinity of the conjugates in a tibia injection model. Using ovariectomized (OVX) rats, initial (3 h) retention of BSA and aminoBP-BSA were found to be equivalent when injected into the medullary cavity of tibia. After 1 day, an 8- and 12-fold higher tibiae retention of the protein was obtained in normal and OVX rats as a result of aminoBP conjugation. A similar result (similar to 12-fold difference) was also obtained in OVX rats after 3 days. We concluded that aminoBP conjugation to BSA imparted a high bone affinity and enhanced bone retention of proteins in normal and OVX rats.