INSULIN-LIKE GROWTH FACTOR-I HORMONAL-REGULATION BY GROWTH-HORMONE AND BY 1,25(OH)2D3 AND ACTIVITY ON HUMAN OSTEOBLAST-LIKE CELLS IN SHORT-TERM CULTURES
INSULIN-LIKE GROWTH FACTOR-I HORMONAL-REGULATION BY GROWTH-HORMONE AND BY 1,25(OH)2D3 AND ACTIVITY ON HUMAN OSTEOBLAST-LIKE CELLS IN SHORT-TERM CULTURES
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DOI：
10.1016/8756-3282(90)90054-3
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发表时间：
1990-01-01
期刊：
影响因子：
4.1
通讯作者：
DELMAS, PD
中科院分区：
文献类型：
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作者：
CHENU, C;VALENTINOPRAN, A;DELMAS, PD
IGF-1已被证明在一些组织中局部产生，并在细胞活动的调节中发挥作用。我们研究了其在人骨源性细胞短期培养中的产生，以及生长激素（GH）和1,25二羟基维生素D3 （1,25(OH)2D3）对这种产生的调节。从外科骨活检中获得的骨细胞在其培养基中产生并分泌IGF-1。在骨源性细胞培养4天后，重组人r-IGF-1浓度为20 ng/mL，增加了碱性磷酸酶活性和骨钙素（骨玻璃蛋白）分泌，这是骨形成的两种特异性标志物。这种刺激仅在125 (OH)2D3存在时发生。暴露于生长激素的人骨细胞碱性磷酸酶活性增加，但未检测到骨钙素。然而，在1,25(OH)2D3 （1 nM）存在的情况下，生长激素浓度为8至40 nM时，人骨细胞的碱性磷酸酶活性增加30-50%，骨钙素分泌增加50 - 100%。在相同浓度下，生长激素也使细胞培养上清中内源性IGF-1水平增加140%，1,25(OH)2D3 （10 nM）也增加了人骨细胞上清中时间和剂量依赖性的IGF-1水平，并刺激了剂量依赖性碱性磷酸酶活性和骨钙素分泌。因此，通过调节局部生长因子如IGF-1、GH和1,25(OH)2D3的产生可能调节人骨细胞的代谢。
IGF-1 has been shown to be locally produced in several tissues and to play a role in the regulation of cellular activity. We have investigated its production in short-term cultures of human bone derived cells, and the regulation of this production by growth hormone (GH) and by 1,25 dihydroxyvitamin D3 (1,25(OH)2D3). Bone cells obtained from surgical bone biopsies produced and secreted IGF-1 in their culture media. In four days cultures of bone-derived cells recombinant human r-IGF-1 at 20 ng/mL increased the alkaline phosphatase activity and the osteocalcin (bone gla protein) secretion, two specific markers of bone formation. This stimulation occurred only in the presence of 1,25(OH)2D3. Human bone cells exposed to GH increased their alkaline phosphatase activity, but no osteocalcin was detectable. However, in the presence of 1,25(OH)2D3 (1 nM), GH in concentrations of 8 to 40 nM increased by 30-50% the alkaline phosphatase activity and by 50 to 100% the osteocalcin secretion of human bone cells. At the same concentrations, GH also increased by 140% endogenous IGF-1 levels in cell culture supernatants, 1,25(OH)2D3 (10 nM) also increased time- and dose-dependently, IGF-1 levels in human bone cell supernatants, and stimulated dose-dependently alkaline phosphatase activity and osteocalcin secretion. It is therefore suggested that by regulating local production of growth factors such as IGF-1, GH and 1,25(OH)2D3 may modulate the metabolism of human bone cells.