EFFECT OF INSULIN-LIKE GROWTH FACTOR-I ON DNA AND PROTEIN-SYNTHESIS IN CULTURED RAT CALVARIA
EFFECT OF INSULIN-LIKE GROWTH FACTOR-I ON DNA AND PROTEIN-SYNTHESIS IN CULTURED RAT CALVARIA
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DOI：
10.1172/jci109908
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发表时间：
1980-01-01
影响因子：
15.9
通讯作者：
CANALIS, E
中科院分区：
文献类型：
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作者：
CANALIS, E
胰岛素样生长因子I （IGF I）是一种生长激素依赖性肽或生长激素，通过检测21天胎鼠颅骨中DNA、胶原蛋白和非胶原蛋白的合成来研究其对骨形成的影响。IGF I在0.1-100 nM浓度下引起[3H]胸腺嘧啶掺入DNA的剂量依赖性刺激；作用时间为6 h， 12 h达到最大，持续时间为96 h。IGF - 1也增加了骨DNA含量。IGF - 1在0.1-3 nM时对[3H]脯氨酸并入胶原酶可消化蛋白（CDP）有较小的刺激作用，而在30 nM时可使[3H]脯氨酸增加2 -3倍，且效果最大。对非胶原蛋白（NCP）标记的影响较小。CDP和NCP的作用在12 h后出现并达到最大，持续96 h。IGF I增加了骨总胶原含量。IGF - 1对[3H]胸腺嘧啶掺入的刺激作用在骨膜和无骨膜骨中均可见，而对CDP标记的刺激作用仅在中心、成骨细胞丰富的非骨膜骨中可见。组织学切片显示，在IGF - 1处理的骨骼中，秋碱阻滞后有丝分裂指数增加了10倍；有丝分裂均匀分布于骨膜和颅骨中部。胰岛素对[3H]脯氨酸在1 nM-1 μ m范围内并入CDP和NCP有促进作用。1 .高胰岛素浓度(0.1和1。M)需要增加[3H]胸腺嘧啶的掺入，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]脯氨酸并入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]胸腺嘧啶的掺入，并可添加到IGF I中。三碘甲状腺原氨酸不影响CDP的标记，但甲状旁腺激素抑制CDP的标记，并与IGF I的作用相反。IGF I和胰岛素对骨胶原的合成有相似的影响，但IGF I在生理浓度下刺激DNA的合成，而胰岛素则没有。
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 day 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 2 to 3-fold 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, nonperiosteal 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 at 1 nM-1 .mu.M similar to the effect of IGF I. high insulin concentrations (0.1 and 1 .mu.M) 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. 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.