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Pertussis toxin‐sensitive Gαi protein and ERK‐dependent pathways mediate ultrasound promotion of osteogenic transcription in human osteoblasts 1
Author(s) -
Chen Yeung-Jen,
Wang Ching-Jen,
Yang Kuender D,
Chang Per-Rong,
Huang Hui-Chen,
Huang Yu-Ting,
Sun Yi-Chih,
Wang Feng-Sheng
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01157-8
Subject(s) - mapk/erk pathway , runx2 , pertussis toxin , microbiology and biotechnology , cholera toxin , osteocalcin , osteoblast , chemistry , signal transduction , protein kinase a , kinase , stimulation , mechanosensitive channels , biology , g protein , endocrinology , receptor , alkaline phosphatase , ion channel , biochemistry , in vitro , enzyme
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/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 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.