Uludag H, Gao T, Wohl G R, Kantoci D, Zernicke R F
Department of Biomedical Engineering, 1098 EDC Building, Faculty of Medicine, University of Alberta, Edmonton, Alberta T6G 2V2, Canada.
Biotechnol Prog. 2000 Nov-Dec;16(6):1115-8. doi: 10.1021/bp000066y.
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 ( approximately 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.
能够刺激骨形成的生长因子是治疗骨质疏松症的潜在治疗药物。然而，至关重要的是，要将靶向机制纳入生长因子中，以便将它们沉积在骨组织中，同时尽量减少向骨骼外部位的分布。为此，已开发出一种策略，即将一种趋骨性分子1-氨基-1,1-二膦酸甲烷（氨基BP）与一种模型蛋白牛血清白蛋白（BSA）进行化学偶联。本研究旨在评估偶联物在胫骨注射模型中的骨亲和力。使用去卵巢（OVX）大鼠，当将BSA和氨基BP-BSA注入胫骨骨髓腔时，发现初始（3小时）保留率相当。1天后，由于氨基BP偶联，正常大鼠和OVX大鼠胫骨中该蛋白的保留率分别提高了8倍和12倍。3天后，OVX大鼠也得到了类似的结果（相差约12倍）。我们得出结论，氨基BP与BSA偶联赋予了正常大鼠和OVX大鼠中的蛋白质高骨亲和力并增强了其在骨中的保留率。
