BACKGROUND Imbalance 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. OBJECTIVES To elucidate the link between EMFs and P2X7 expression and investigate its potential as a novel therapeutic target in osteoporosis. METHOD We 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. RESULTS EMF 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. CONCLUSIONS EMF 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.

中文翻译：

---

电磁场处理在成骨诱导下增加间充质干细胞中嘌呤能受体P2X7的表达并激活其下游Akt /GSK3β/β-catenin轴。

背景技术骨形成和吸收的失衡是导致骨质疏松的病理过程的重要组成部分。尽管尚未完全阐明确切的机制，但据报道电磁场（EMF）有益于成骨。嘌呤能受体P2X7在成骨细胞中表达，据报道参与骨代谢的调节。目的阐明EMF与P2X7表达之间的联系，并研究其作为骨质疏松症新型治疗靶标的潜力。方法我们研究了EMF对人骨髓间充质干细胞（h-MSCs）P2X7表达和下游信号传导的影响。我们还建立了卵巢切除（OVX）骨质疏松大鼠模型，以评估将EMF与P2X7激动剂联合使用的治疗效果。结果EMF处理在成骨诱导条件下增加了h-MSCs中P2X7的表达，但在常规培养条件下却没有。P2X7或PI3K / Akt抑制作用部分抑制了EMF的促成骨作用，并降低了Akt /GSK3β/β-catenin轴的EMF刺激活性。在同时抑制P2X7和PI3K / Akt之后，未观察到这种抑制作用的累加效应。与单独使用EMF处理相比，在P2X7激动剂存在下进行EMF处理在增加成骨标记物表达方面具有更大的作用。在OVX骨质疏松症模型中，将EMF与P2X7激动剂联合使用的治疗效果优于单独的EMF治疗。结论EMF处理可在成骨分化过程中增加h-MSC的P2X7表达，从而激活Akt /GSK3β/β-catenin轴，促进成骨。我们的发现还表明，EMF和P2X7激动剂联合治疗可能是骨质疏松症治疗的有效新策略。