Pertussis toxin-sensitive Gαi protein and ERK-dependent pathways mediate ultrasound promotion of osteogenic transcription in human osteoblasts
Pertussis toxin-sensitive Gαi protein and ERK-dependent pathways mediate ultrasound promotion of osteogenic transcription in human osteoblasts
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DOI：
10.1016/s0014-5793(03)01157-8
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发表时间：
2003-11-06
期刊：
影响因子：
3.5
通讯作者：
Wang, FS
中科院分区：
文献类型：
--
作者：
Chen, YJ;Wang, CJ;Wang, FS
骨细胞通过机械感受器对机械刺激作出反应，并将生物物理刺激转化为改变基因表达和细胞适应的生化信号。脉冲声能治疗提高膜电位，诱导成骨活动。膜结合成骨细胞机械感受器如何将物理超声（US）刺激转化为成骨反应尚不完全清楚。我们证明了低强度脉冲US处理（200-mus脉冲，1 kHz, 30 mW/cm(2)）升高Cbfa1/Runx2 mRNA表达，并逐渐促进人成骨细胞骨钙素mRNA表达。百日咳毒素（PTX）预处理，而不是霍乱毒素预处理，抑制了us增强的成骨转录。这表明Gi蛋白而非Gs蛋白参与了US对成骨转录的促进。进一步的研究表明，US处理可以迅速增加ptx敏感的Galphai蛋白水平，随后增强细胞外信号调节激酶（ERK）的磷酸化。PTX预处理显著降低了US对ERK活化的促进。此外，PD98059抑制ERK活性可抑制Cbfa1/Runx2和骨钙素mRNA表达的增加。膜状Galphai蛋白和胞质ERK通路在成骨细胞对脉冲美国刺激的反应中作为强有力的机械敏感信号。(C) 2003年欧洲生化学会联合会。Elsevier B.V.版权所有。
Bone cells respond to mechanical stimulation via mechanoreceptors and convert biophysical stimulation into biochemical signals that alter gene expression and cellular adaptation. Pulsed acoustic energy treatment raises membrane potential and induces osteogenic activity. How membrane-bound osteoblast mechanoreceptors convert physical ultrasound (US) stimuli into osteogenic responses is not fully understood. We demonstrated that low-intensity pulsed US treatment (200-mus pulse, 1 kHz, 30 mW/cm(2)) elevated Cbfa1/Runx2 mRNA expression and progressively promoted osteocalcin mRNA expression in human osteoblasts. Pretreatment with pertussis toxin (PTX), but not with cholera toxin, suppressed US-augmented osteogenic transcription. This indicated that Gi proteins, but not Gs proteins, were involved in US promotion of osteogenic transcription. Further studies demonstrated US treatment could rapidly increase PTX-sensitive Galphai protein levels and subsequently enhanced phosphorylation of extracellular signal-regulated kinase (ERK). PTX pretreatment significantly reduced US promotion of ERK activation. Moreover, inhibition of ERK activity by PD98059 suppressed US augmentation of Cbfa1/Runx2 and osteocalcin mRNA expression. Membranous Galphai proteins and cytosolic ERK pathways acted as potent mechanosensitive signals in the response of osteoblasts to pulsed US stimulation. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.