Lean J M, Mackay A G, Chow J W, Chambers T J
Department of Histopathology, St. George's Hospital Medical School, London, United Kingdom.
Am J Physiol. 1996 Jun;270(6 Pt 1):E937-45. doi: 10.1152/ajpendo.1996.270.6.E937.
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.
我们分析了在骨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，其调节紊乱会特异性影响骨骼）的表达情况。在成骨刺激后30分钟内，这两个基因在受到机械刺激的骨的骨细胞中强烈表达，而在对照骨中则未表达。IGF-I mRNA表达在6小时内持续增加，且仅限于骨细胞，并被吲哚美辛强烈抑制。虽然早期IGF-I mRNA表达对放线菌酮有抗性，但6小时后有一定程度的抑制，这增加了IGF-I表达可能通过自分泌机制延长的可能性。c-fos mRNA在骨细胞和骨表面均增加。在这两个部位，c-fos表达都是短暂的，可被放线菌酮延长，并且即使在存在吲哚美辛的情况下也受到强烈刺激。因此，骨细胞对机械刺激的反应是IGF-I立即延长表达和c-fos立即短暂表达，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对吲哚美辛的敏感性表明，在此过程中骨细胞中至少有两条信号通路被激活。
