Bone fracture is a growing public health burden and there is a clinical need for non-invasive therapies to aid in the fracture healing process. Previous studies have demonstrated the utility of electromagnetic (EM) fields in promoting bone repair; however, its underlying mechanism of action is unclear. Interestingly, there is a growing body of literature describing positive effects of an EM field on mitochondria. In our own work, we have previously demonstrated that differentiation of osteoprogenitors into osteoblasts involves activation of mitochondrial oxidative phosphorylation (OxPhos). Therefore, it was reasonable to propose that EM field therapy exerts bone anabolic effects via stimulation of mitochondrial OxPhos. In this study, we show that application of a low intensity constant EM field source on osteogenic cells in vitro resulted in increased mitochondrial membrane potential and respiratory complex I activity and induced osteogenic differentiation. In the presence of mitochondrial inhibitor antimycin A, the osteoinductive effect was reversed, confirming that this effect was mediated via increased OxPhos activity. Using a mouse tibial bone fracture model in vivo, we show that application of a low intensity constant EM field source enhanced fracture repair via improved biomechanical properties and increased callus bone mineralization. Overall, this study provides supporting evidence that EM field therapy promotes bone fracture repair through mitochondrial OxPhos activation.

骨折是一个日益严重的公共健康负担，临床需要非侵入性疗法来帮助骨折愈合过程。先前的研究已经证明了电磁 (EM) 场在促进骨修复方面的效用；然而，其潜在的作用机制尚不清楚。有趣的是，越来越多的文献描述了电磁场对线粒体的积极影响。在我们自己的工作中，我们之前已经证明骨祖细胞向成骨细胞的分化涉及线粒体氧化磷酸化 (OxPhos) 的激活。因此，提出 EM 场疗法通过刺激线粒体 OxPhos 发挥骨合成代谢作用是合理的。在这项研究中，我们表明，在体外对成骨细胞应用低强度恒定电磁场源导致线粒体膜电位和呼吸复合体 I 活性增加，并诱导成骨分化。在线粒体抑制剂抗霉素 A 的存在下，骨诱导作用被逆转，证实这种作用是通过增加的 OxPhos 活性介导的。使用体内小鼠胫骨骨折模型，我们表明应用低强度恒定电磁场源通过改善生物力学特性和增加愈伤组织骨矿化来增强骨折修复。总的来说，这项研究提供了支持证据，证明 EM 场疗法通过线粒体 OxPhos 激活促进骨折修复。