Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/117442
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Type: Journal article
Title: Pulsed electromagnetic fields promote bone formation by activating the sAC–cAMP–PKA–CREB signaling pathway
Author: Wang, Y.
Pu, X.
Shi, W.
Fang, Q.
Chen, X.
Xi, H.
Gao, Y.
Zhou, J.
Xian, C.
Chen, K.
Citation: Journal of Cellular Physiology, 2019; 234(3):2807-2821
Publisher: Wiley
Issue Date: 2019
ISSN: 0021-9541
1097-4652
Statement of
Responsibility: 
Yuan‐Yuan Wang, Xiu‐Ying Pu, Wen‐Gui Shi, Qing‐Qing Fang, Xin‐Ru Chen, Hui‐Rong Xi, Yu‐Hai Gao, Jian Zhou, Cory J. Xian, Ke‐Ming Chen
Abstract: The application of pulsed electromagnetic fields (PEMFs) in the prevention and treatment of osteoporosis has long been an area of interest. However, the clinical application of PEMFs remains limited because of the poor understanding of the PEMF action mechanism. Here, we report that PEMFs promote bone formation by activating soluble adenylyl cyclase (sAC), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and cAMP response element-binding protein (CREB) signaling pathways. First, it was found that 50 Hz 0.6 millitesla (mT) PEMFs promoted osteogenic differentiation of rat calvarial osteoblasts (ROBs), and that PEMFs activated cAMP-PKA-CREB signaling by increasing intracellular cAMP levels, facilitating phosphorylation of PKA and CREB, and inducing nuclear translocation of phosphorylated (p)-CREB. Blocking the signaling by adenylate cyclase (AC) and PKA inhibitors both abolished the osteogenic effect of PEMFs. Second, expression of sAC isoform was found to be increased significantly by PEMF treatment. Blocking sAC using sAC-specific inhibitor KH7 dramatically inhibited the osteogenic differentiation of ROBs. Finally, the peak bone mass of growing rats was significantly increased after 2 months of PEMF treatment with 90 min/day. The serum cAMP content, p-PKA, and p-CREB as well as the sAC protein expression levels were all increased significantly in femurs of treated rats. The current study indicated that PEMFs promote bone formation in vitro and in vivo by activating sAC-cAMP-PKA-CREB signaling pathway of osteoblasts directly or indirectly.
Keywords: PEMFs; bone formation; cAMP; osteoblast; soluble AC
Rights: © 2018 Wiley Periodicals, Inc.
RMID: 0030102902
DOI: 10.1002/jcp.27098
Grant ID: http://purl.org/au-research/grants/nhmrc/1042105
Appears in Collections:Psychology publications

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