Abstract
BackgroundImbalance in bone formation and resorption is a crucial component of the pathological process leading to osteoporosis. Electromagnetic fields (EMFs) have been reported to be beneficial to osteogenesis, although the exact mechanism has not been fully clarified. Purinergic receptor P2X7 is expressed in osteoblasts and is reported to participate in the regulation of bone metabolism.ObjectivesTo elucidate the link between EMFs and P2X7 expression and investigate its potential as a novel therapeutic target in osteoporosis.MethodWe investigated the effect of EMFs on P2X7 expression and downstream signaling in human bone marrow mesenchymal stem cells (h-MSCs). We also established an ovariectomized (OVX) osteoporosis rat model to evaluate the therapeutic efficacy of combining EMFs with P2X7 agonists.ResultsEMF treatment increased P2X7 expression in h-MSCs under conditions of osteogenic induction but not under regular culture conditions. P2X7 or PI3K/Akt inhibition partially inhibited the pro-osteogenic effect of EMF and lowered the EMF-stimulated activity of the Akt/GSK3β/β-catenin axis. No additive effect of this suppression was observed following simultaneous inhibition of P2X7 and PI3K/Akt. EMF treatment in the presence of a P2X7 agonist had a greater effect in increasing osteogenic marker expression than that of EMF treatment alone. In the OVX osteoporosis model, the therapeutic efficacy of combining EMFs with P2X7 agonists was superior to that of EMF treatment alone.ConclusionsEMF treatment increases P2X7 expression by h-MSCs during osteogenic differentiation, leading to activation of the Akt/GSK3β/β-catenin axis, which promotes the osteogenesis. Our findings also indicate that combined EMF and P2X7 agonist treatment may be an effective novel strategy for osteoporosis therapy.
Highlights
Osteoporosis, which literally means porous bone, is a disease in which the density and quality of bone are reduced
Our findings indicate that combined Electromagnetic fields (EMFs) and Purinergic receptor P2X7 (P2X7) agonist treatment may be an effective novel strategy for osteoporosis therapy
Under osteogenic culture conditions, human bone marrow mesenchymal stem cells (h-MSCs) expression of P2X7 mRNA was slightly increased on day 3 and was increased by more than twofold on days 7 to 21. This effect was significantly enhanced by exposure to EMFs. Human bone marrow mesenchymal stem cells (hMSCs) cultured in osteogenic medium combined with EMF exposure exhibited a marked increase (80%) in P2X7 mRNA expression on day 3, with further increases in P2X7 expression detected on days 7 to 21 (Fig. 2a)
Summary
Osteoporosis, which literally means porous bone, is a disease in which the density and quality of bone are reduced. There are millions of osteoporosis patients worldwide, most of which are postmenopausal women. It is characterized by reduced bone mass and micro-architectural degradation of bone tissue, resulting in increased bone fragility and higher fracture risk [1]. Uncoupling between osteoblast and osteoclast activity and/ or loss of the balance between osteogenic differentiation and adipogenic differentiation of BMSCs lead to osteoporosis. Imbalance in bone formation and resorption is a crucial component of the pathological process leading to osteoporosis. Purinergic receptor P2X7 is expressed in osteoblasts and is reported to participate in the regulation of bone metabolism
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
