Pertussis toxin‐sensitive Gαi protein and ERK‐dependent pathways mediate ultrasound promotion of osteogenic transcription in human osteoblasts

FEBS Letters

Chang, Per-Rong³  Huang, Yu-Ting²  Huang, Hui-Chen²  Sun, Yi-Chih²  Wang, Feng-Sheng²  Yang, Kuender D²  Wang, Ching-Jen¹  Chen, Yeung-Jen⁴ 

[1] Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan;Department of Medical Research, Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan;Fooyin Universtiy, Ta-Liao, Kaohsiung, Taiwan;Department of Orthopedic Surgery, Chang Gung University, Linkou, Taiwan

关键词: Osteoblast;    Pertussis toxin;    Gαi protein;    Extracellular signal-regulated kinase;    Cbfa1/Runx2;    Low-intensity pulsed ultrasound;   

DOI  :  10.1016/S0014-5793(03)01157-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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-μs pulse, 1 kHz, 30 mW/cm²) 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 Gαi 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 Gαi proteins and cytosolic ERK pathways acted as potent mechanosensitive signals in the response of osteoblasts to pulsed US stimulation.

【 授权许可】

Unknown