Author: Wang YY1,2, Pu XY1, Shi WG2, Fang QQ2, Chen XR3, Xi HR2, Gao YH2, Zhou J2, Xian CJ4, Chen KM2
Affiliation: <sup>1</sup>Department of Bioengineering, School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou, China.
<sup>2</sup>Institute of Orthopaedics, Lanzhou General Hospital of CPLA, Lanzhou, China.
<sup>3</sup>Department of Biology, College of Life Sciences, Northwest A & F University, Yanglin, China.
<sup>4</sup>Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
Conference/Journal: J Cell Physiol.
Date published: 2018 Aug 1
Other:
Special Notes: doi: 10.1002/jcp.27098. [Epub ahead of print] , Word Count: 233
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
PMID: 30067871 DOI: 10.1002/jcp.27098