Richman C, Baylink D J, Lang K, Dony C, Mohan S
J.L. Pettis Veterans Administration Medical Center and Loma Linda University, California 92357, USA.
Endocrinology. 1999 Oct;140(10):4699-705. doi: 10.1210/endo.140.10.7081.
Insulin-like growth factor-binding protein-5 (rhIGFBP-5) is stored in bone and stimulates osteoblast cell proliferation in vitro. Bone formation is dependent on the number and activity of osteoblasts. We therefore evaluated the ability of recombinant human (rh) IGFBP-5 to increase osteoblast activity in vitro; both alkaline phosphatase (ALP) activity and osteocalcin levels showed a dose-dependent increase. In in vivo time-course studies, daily s.c. administration of 50 microg rhIGFBP-5/day/mouse significantly increased serum osteocalcin levels by day 7, and these levels were sustained through day 21. We further evaluated whether rhIGFBP-5 was as effective as IGF-I. Daily s.c. administration of rhIGFBP-5 (50 microg/day), IGF-I (13 microg/day), or IGF-I plus rhIGFBP-5 complex for 9 days increased serum osteocalcin levels by 58%, 65%, and 81% (P < 0.001 in all) and femoral bone extract ALP activity by 85% (P < 0.001), 29% (P < 0.05), and 13% (P = NS), respectively, and decreased carboxyl-terminal cross-linked telopeptide of type I collagen by 29% (P < 0.05), 20% (P = NS), and 12.5% (P = NS), respectively. One s.c. injection of rhIGFBP-5 (50 microg/mouse) increased serum osteocalcin and bone ALP activity by 21% (P < 0.05) and 27% (P < 0.02), respectively, after 5 days, but did not significantly increase serum IGF-I (1, 6, or 24 h/postinjection), suggesting that the effects of rhIGFBP-5 on bone are not mediated by increasing circulating IGF-I. Our data demonstrate that systemic administration of rhIGFBP-5, either alone or in combination with IGF-I, increases bone formation parameters in vivo.
胰岛素样生长因子结合蛋白-5（rhIGFBP-5）储存于骨骼中，并在体外刺激成骨细胞增殖。骨形成取决于成骨细胞的数量和活性。因此，我们评估了重组人（rh）IGFBP-5在体外增强成骨细胞活性的能力；碱性磷酸酶（ALP）活性和骨钙素水平均呈剂量依赖性增加。在体内时间进程研究中，每天皮下注射50μg rhIGFBP-5/天/小鼠，到第7天时血清骨钙素水平显著升高，且这些水平持续至第21天。我们进一步评估了rhIGFBP-5是否与IGF-I一样有效。每天皮下注射rhIGFBP-5（50μg/天）、IGF-I（13μg/天）或IGF-I加rhIGFBP-5复合物9天，血清骨钙素水平分别升高58%、65%和81%（所有P均<0.001），股骨骨提取物ALP活性分别升高85%（P<0.001）、29%（P<0.05）和13%（P=无显著性差异），I型胶原羧基末端交联肽分别降低29%（P<0.05）、20%（P=无显著性差异）和12.5%（P=无显著性差异）。单次皮下注射rhIGFBP-5（50μg/小鼠）5天后，血清骨钙素和骨ALP活性分别升高21%（P<0.05）和27%（P<0.02），但未显著升高血清IGF-I（注射后1、6或24小时），这表明rhIGFBP-5对骨骼的作用不是通过增加循环中的IGF-I介导的。我们的数据表明，全身给予rhIGFBP-5，单独或与IGF-I联合使用，均可在体内增加骨形成参数。
