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Pulsed electromagnetic fields promote bone formation by activating the sAC-cAMP-PKA-CREB signaling pathway.
Pulsed electromagnetic fields promote bone formation by activating the sAC-cAMP-PKA-CREB signaling pathway.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 2019 Mar; Vol. 234 (3), pp. 2807-2821. Date of Electronic Publication: 2018 Aug 01. - Publication Year :
- 2019
-
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.<br /> (© 2018 Wiley Periodicals, Inc.)
- Subjects :
- Adenylyl Cyclase Inhibitors pharmacology
Adenylyl Cyclases genetics
Adenylyl Cyclases pharmacology
Animals
Bone Density radiation effects
Cell Differentiation radiation effects
Cyclic AMP antagonists & inhibitors
Cyclic AMP genetics
Cyclic AMP Response Element-Binding Protein genetics
Cyclic AMP-Dependent Protein Kinases antagonists & inhibitors
Cyclic AMP-Dependent Protein Kinases genetics
Disease Models, Animal
Femur growth & development
Femur pathology
Femur radiation effects
Gene Expression Regulation drug effects
Gene Expression Regulation radiation effects
Humans
Osteoblasts radiation effects
Osteoporosis genetics
Osteoporosis pathology
Rats
Signal Transduction radiation effects
Enzyme Inhibitors pharmacology
Magnetic Field Therapy
Osteogenesis radiation effects
Osteoporosis therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4652
- Volume :
- 234
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 30067871
- Full Text :
- https://doi.org/10.1002/jcp.27098