Effects of systemic and local administration of recombinant human IGF-I (rhIGF-I) on de novo bone formation in an aged mouse model
Effects of systemic and local administration of recombinant human IGF-I (rhIGF-I) on de novo bone formation in an aged mouse model
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DOI：
10.1359/jbmr.060618
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发表时间：
2006-09-01
影响因子：
6.2
通讯作者：
Lumpkin, Charles K., Jr.
中科院分区：
文献类型：
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作者：
Fowlkes, John L.;Thrailkill, Kathryn M.;Lumpkin, Charles K., Jr.
人类和啮齿动物研究支持igf - 1在骨形成中的主要作用。内分泌和旁分泌/自分泌igf - 1在正常成骨细胞发生和骨形成中都有重要作用。我们使用牵张成骨（DO）小鼠模型，评估了持续给药重组人（rh）IGF-I（局部递送或全身吸收）对老年小鼠模型骨形成的影响。材料与方法：老龄小鼠（18月龄C57BL/6雄性小鼠）进行DO，每天0.15 mm分心。截骨时，皮下插入微渗透泵(1)皮下递送载体或rhIGF-I进行全身递送，或(2)通过从泵到牵张部位的皮下输液管将载体或rhIGF-I直接递送到新形成的骨。在研究结束时测定小鼠IGF-I、人IGF-I和骨钙素的血清浓度。结果：无论给药途径如何，在DO间隙观察到的新骨形成显示，rhigf - i处理小鼠的新骨形成显著增加。然而，人类igf - 1的可检测水平仅在全身接受rhigf - 1的动物血清中发现。骨钙素水平在对照组和rhggf - i治疗组之间没有差异。结论：在新骨形成通常明显受损的老年小鼠模型中，局部和全身递送rhIGF-I都能显著增加新骨形成，表明rhIGF-I可能改善老年性骨质疏松症。由于全身给药igf - 1可能导致不良的副作用，包括增加患癌症的风险，局部给药igf - 1改善骨再生而不增加循环igf - 1水平的研究结果表明，这种给药途径可能更适合高危的老年人群。
Introduction: Human and rodent research supports a primary role for IGF-I in bone formation. Significant roles for both endocrine and paracrine/autocrine IGF-I have been suggested for normal osteoblastogenesis and bone formation. We have assessed, using a mouse model of distraction osteogenesis (DO), the impact of continuous administration of recombinant human (rh)IGF-I, delivered either locally to the distraction site or absorbed systemically, on bone formation in an aged mouse model.Materials and Methods: DO was performed in aged mice (18-month-old C57BL/6 male mice), which were distracted at 0.15 mm daily. At the time of osteotomy, miniosmotic pumps were inserted subcutaneously to (1) deliver vehicle or rhIGF-I subcutaneously for systemic delivery or (2) deliver vehicle or rhIGF-I directly to the newly forming bone through infusion tubing routed subcutaneously from the pump to the distraction site. Serum concentrations of mouse IGF-I, human IGF-I, and osteocalcin were determined at the end of the study.Results: New bone formation observed in DO gaps showed a significant increase in new bone formation in rhIGF-I-treated mice, irrespective of delivery route. However, detectable levels of human IGF-I were found only in the serum of animals receiving rhIGF-I systemically. Osteocalcin levels did not differ between controls and rhlGF-I-treated groups.Conclusions: Locally and systemically delivered rhIGF-I both produce significant increases in new bone formed in an aged mouse model in which new bone formation is normally markedly impaired, suggesting that rhIGF-I may improve senile osteoporosis. Because systemic administration of IGF-I can result in untoward side effects, including an increased risk for cancer, the findings that locally delivered IGF-I improves bone regeneration without increasing circulating IGF-I levels suggests that this delivery route may be preferable in an at-risk, aged population.