Osteocytic expression of mRNA for c-fos and IGF-I: An immediate early gene response to an osteogenic stimulus
Osteocytic expression of mRNA for c-fos and IGF-I: An immediate early gene response to an osteogenic stimulus
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DOI：
10.1152/ajpendo.1996.270.6.e937
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发表时间：
1996-06-01
影响因子：
5.1
通讯作者：
Chambers, TJ
中科院分区：
文献类型：
--
作者：
Lean, JM;Mackay, AG;Chambers, TJ
我们分析了在骨骼对机械刺激的成骨反应过程中，胰岛素样生长因子 I (IGF-I)（一种与骨形成有关的生长因子）和 c-fos（一种原癌基因，其中紊乱的调节特别影响骨骼）的表达。在成骨刺激后 30 分钟内，这两个基因在机械刺激的骨细胞中强烈表达，但在控制骨中不表达。 IGF-I mRNA 表达增加长达 6 小时，仅限于骨细胞，并被吲哚美辛强烈抑制。尽管早期 IGF-I mRNA 表达对放线菌酮具有抗性，但 6 小时后出现一定程度的抑制，这增加了 IGF-I 表达可能通过自分泌机制延长的可能性。骨细胞和骨表面的 c-fos mRNA 均增加。在这两个位点，c-fos 的表达都是短暂的，可以被放线菌酮延长，并且即使在吲哚美辛存在下也能被强烈刺激。因此，骨细胞对机械刺激做出反应，并立即延长 IGF-I 表达和立即瞬时表达 c-fos，这表明骨细胞参与了对机械刺激的成骨反应。此外，c-fos和IGF-I基因表达的不同空间分布和吲哚美辛敏感性表明，在此过程中骨细胞中至少有两条信号通路被激活。
We analyzed the expression, during the osteogenic response of bone to mechanical stimulation, of insulin-like growth factor I (IGF-I), a growth factor implicated in bone formation, and c-fos, a protooncogene in which disordered regulation specifically affects bone. Both genes were strongly expressed in osteocytes of mechanically stimulated but not control bones within 30 min of the osteogenic stimulus. IGF-I mRNA expression increased up to 6 h, was restricted to osteocytes, and was strongly suppressed by indomethacin. Although early IGF-I mRNA expression was resistant to cycloheximide, there was a degree of suppression after 6 h, raising the possibility that IGF-I expression might be prolonged by autocrine mechanisms. c-fos mRNA was increased both in osteocytes and on bone surfaces. At both sites, c-fos expression was transient, prolonged by cycloheximide, and was strongly stimulated even in the presence of indomethacin. Thus osteocytes respond to mechanical stimulation with immediate prolonged expression of IGF-I and immediate transient expression of c-fos, implicating osteocytes in the osteogenic response to mechanical stimulation. Moreover, the different spatial distribution and indomethacin sensitivity of c-fos and IGF-I gene expression suggest that at least two signaling pathways are activated in osteocytes during this process.