Reich K M, Frangos J A
Department of Chemical Engineering, Pennsylvania State University, University Park 16802.
Am J Physiol. 1991 Sep;261(3 Pt 1):C428-32. doi: 10.1152/ajpcell.1991.261.3.C428.
Osteoblasts in culture respond to mechanical strains. Fluid flow has been shown to increase intracellular adenosine 3',5'-cyclic monophosphate levels in cultured osteoblasts, and this response is mediated by prostaglandin synthesis. The signal transduction pathway of these cells exposed to fluid flow is still unknown. In the present study, we have demonstrated a 9- and 20-fold increase in the rate of prostaglandin E2 (PGE2) production in osteoblasts exposed to low (6 dyn/cm2) and high (24 dyn/cm2) steady shear, respectively. We further observed that fluid flow induced increases in the intracellular levels of inositol trisphosphate (IP3), another important second messenger. A shear stress of 24 dyn/cm2 increased IP3 levels dramatically for up to 2 h. Removal of flow resulted in a gradual return of IP3 to basal levels. The stimulation of IP3 levels was partially inhibited by 20 microM ibuprofen and 14 microM indomethacin, indicating that the IP3 response was partly dependent on flow-induced prostaglandin synthesis. The IP3 response was unaffected by daltroban, a specific thromboxane antagonist. These results show that fluid flow induced prostaglandin E2 production and increased intracellular levels of IP3 in osteoblasts. This suggests that flow may be the external signal produced by loading and that these messengers may be involved in the transduction of mechanical strain into a biochemical response.
培养中的成骨细胞对机械应变有反应。已表明流体流动可增加培养的成骨细胞内3',5'-环磷酸腺苷水平，且这种反应由前列腺素合成介导。这些细胞暴露于流体流动时的信号转导途径仍不清楚。在本研究中，我们证明暴露于低（6达因/平方厘米）和高（24达因/平方厘米）稳定剪切力的成骨细胞中前列腺素E2（PGE2）产生速率分别增加了9倍和20倍。我们进一步观察到流体流动诱导另一种重要的第二信使肌醇三磷酸（IP3）的细胞内水平升高。24达因/平方厘米的剪切应力使IP3水平显著升高长达2小时。去除流动导致IP3逐渐恢复到基础水平。20微摩尔布洛芬和14微摩尔吲哚美辛部分抑制了IP3水平的刺激，表明IP3反应部分依赖于流动诱导的前列腺素合成。IP3反应不受特异性血栓素拮抗剂达曲班的影响。这些结果表明流体流动诱导成骨细胞中前列腺素E产生并增加细胞内IP3水平。这表明流动可能是加载产生的外部信号，并且这些信使可能参与将机械应变转化为生化反应。
