Canalis E
J Clin Invest. 1980 Oct;66(4):709-19. doi: 10.1172/JCI109908.
Insulinlike growth Factor I (IGF I), a growth hormone-dependent peptide or somatomedin, was studied for its effects on bone formation by examining the synthesis of DNA, collagen, and noncollagen protein in cultures of 21-d fetal rat calvaria. IGF I caused a dose-dependent stimulation of the incorporation of [3H]thymidine into DNA at concentrations of 0.1--100 nM; the effect appeared after 6 h, was maximal at 12 h, and was sustained for 96 h. IGF I also increased the bone DNA content, IGF I at 0.1--3 nM had a small stimulatory effect on the incorporation of [3H]proline into collagenase-digestible protein (CDP) whereas 30 nM IGF I caused a two- to threefold increment and had a maximal effect. A smaller effect on the labeling of noncollagen protein (NCP) was also observed. The effect of CDP and NCP appeared and was maximal after 12 h and was sustained for 96 h. IGF I increased the total collagen content of bones. The IGF I stimulatory effect on the incorporation of [3H]thymidine was seen in both the periosteum and periosteum-free calvarium, whereas that on the labeling of CDP was seen only in the central, osteoblastic-rich, non-periosteal bone. Histological sections showed a 10-fold increase in the mitotic index after Colcemid arrest in IGF I-treated bones, the mitoses were equally distributed in the periosteum and central portions of the calvarium. Insulin had a stimulatory effect on the incorporation of [3H]proline into CDP and NCP and 1 nM--1 microM similar to the effect of IGF I. In contrast, high insulin concentrations (0.1 and 1 microM) were required to increase the incorporation of [3H]thymidine, and insulin did not affect DNA content. Cortisol decreased the stimulatory effect of IGF I on DNA labeling but greatly enhanced the stimulatory effect of IGF I on the incorporation of [3H]proline into CDP. Triiodothyronine and parathyroid hormone increased the incorporation of [3H]thymidine and were additive to IGF I. Triiodothyronine did not affect the labeling of CDP, but parathyroid hormone inhibited it and opposed the effect of IGF I. These studies indicate that IGF I stimulates bone DNA, collagen, and NCP synthesis in vitro. IGF I and insulin have similar effects on bone collagen synthesis but IGF I stimulates the synthesis of DNA at physiological concentrations, and insulin does not.
胰岛素样生长因子I（IGF I）是一种依赖生长激素的肽或生长调节素，通过检测21日龄胎鼠颅骨培养物中DNA、胶原蛋白和非胶原蛋白的合成，研究了其对骨形成的影响。IGF I在0.1 - 100 nM浓度下对[3H]胸苷掺入DNA有剂量依赖性刺激作用；该作用在6小时后出现，12小时达到最大，并持续96小时。IGF I还增加了骨DNA含量，0.1 - 3 nM的IGF I对[3H]脯氨酸掺入胶原酶可消化蛋白（CDP）有轻微刺激作用，而30 nM的IGF I则使其增加两到三倍并产生最大效应。对非胶原蛋白（NCP）标记的影响较小。CDP和NCP的作用在12小时后出现并达到最大，持续96小时。IGF I增加了骨的总胶原蛋白含量。IGF I对[3H]胸苷掺入的刺激作用在骨膜和无骨膜颅骨中均可见，而对CDP标记的刺激作用仅在富含成骨细胞的中央非骨膜骨中可见。组织学切片显示，在秋水仙碱阻滞的IGF I处理骨中，有丝分裂指数增加了10倍，有丝分裂在骨膜和颅骨中央部分均匀分布。胰岛素对[3H]脯氨酸掺入CDP和NCP有刺激作用，1 nM - 1 microM时与IGF I的作用相似。相比之下，需要高浓度胰岛素（0.1和1 microM）才能增加[3H]胸苷的掺入，且胰岛素不影响DNA含量。皮质醇降低了IGF I对DNA标记的刺激作用，但大大增强了IGF I对[3H]脯氨酸掺入CDP的刺激作用。三碘甲状腺原氨酸和甲状旁腺激素增加了[3H]胸苷的掺入，且与IGF I有相加作用。三碘甲状腺原氨酸不影响CDP标记，但甲状旁腺激素抑制其标记并对抗IGF I的作用。这些研究表明，IGF I在体外刺激骨DNA、胶原蛋白和NCP的合成。IGF I和胰岛素对骨胶原蛋白合成有相似作用，但IGF I在生理浓度下刺激DNA合成，而胰岛素则无此作用。
