Pulsed electromagnetic fields regulate osteocyte apoptosis, RANKL/OPG expression, and its control of osteoclastogenesis depending on the presence of primary cilia.
Pulsed electromagnetic fields regulate osteocyte apoptosis, RANKL/OPG expression, and its control of osteoclastogenesis depending on the presence of primary cilia.
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脉冲电磁场调节骨细胞凋亡、RANKL/OPG 表达及其对破骨细胞生成的控制，具体取决于初级纤毛的存在。
DOI：
10.1002/jcp.27734
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发表时间：
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通讯作者：
Jing D
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作者：
Wang P;Tang C;Wu J;Yang Y;Yan Z;Liu X;Shao X;Zhai M;Gao J;Liang S;Luo E;Jing D
越来越多的证据表明，脉冲电磁场（PEMF）可以调节体内骨代谢，并在体外调节成骨细胞和破骨细胞的活性。骨细胞占骨细胞的95%，是骨骼中主要的机械传感器，用于传导外部机械信号并产生细胞因子来调节成骨细胞和破骨细胞的活动。针对骨细胞信号通路正在成为骨疾病的新兴治疗策略。我们在此系统地研究了骨细胞行为、功能的变化及其对破骨细胞生成的调节响应PEMF。将骨细胞样 MLO-Y4 细胞暴露于不同强度（0、5 和 30 高斯 [G]）的 15 Hz PEMF 刺激 2 小时。我们发现骨细胞的细胞凋亡和细胞骨架组织受到PEMF以强度依赖性的方式调节。此外，5G PEMF暴露显着抑制了MLO-Y4细胞中凋亡相关基因的表达，还抑制了核因子κB受体激活剂配体/骨保护素（RANKL/OPG）比率的基因和蛋白表达。用暴露于PEMF（5 G）的骨细胞的条件培养基处理后，体外破骨细胞的形成、成熟和破骨骨吸收能力显着受到抑制。我们的结果还表明，使用 Polaris siRNA 转染消除骨细胞中的初级纤毛后，5 G PEMF 暴露的骨细胞条件培养基诱导的破骨细胞形成、成熟和骨吸收能力的抑制显着减弱。总之，我们的研究结果强调，5 G 的 PEMF 可以抑制细胞凋亡，调节细胞骨架分布，降低骨细胞中 RANKL/OPG 的表达，还可以抑制骨细胞介导的破骨细胞生成，而破骨细胞生成需要骨细胞中存在初级纤毛。这项研究丰富了我们进一步了解骨细胞生物学行为的基础知识，也有助于更全面地理解电磁刺激对骨骼和相关骨骼疾病（例如骨折和骨质疏松症）的影响机制。
Growing evidence has shown that pulsed electromagnetic fields (PEMF) can modulate bone metabolism in vivo and regulate the activities of osteoblasts and osteoclasts in vitro. Osteocytes, accounting for 95% of bone cells, act as the major mechanosensors in bone for transducing external mechanical signals and producing cytokines to regulate osteoblastic and osteoclastic activities. Targeting osteocytic signaling pathways is becoming an emerging therapeutic strategy for bone diseases. We herein systematically investigated the changes of osteocyte behaviors, functions, and its regulation on osteoclastogenesis in response to PEMF. The osteocyte-like MLO-Y4 cells were exposed to 15 Hz PEMF stimulation with different intensities (0, 5, and 30 Gauss [G]) for 2 hr. We found that the cell apoptosis and cytoskeleton organization of osteocytes were regulated by PEMF with an intensity-dependent manner. Moreover, PEMF exposure with 5 G significantly inhibited apoptosis-related gene expression and also suppressed the gene and protein expression of the receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG) ratio in MLO-Y4 cells. The formation, maturation, and osteoclastic bone-resorption capability of in vitro osteoclasts were significantly suppressed after treated with the conditioned medium from PEMF-exposed (5 G) osteocytes. Our results also revealed that the inhibition of osteoclastic formation, maturation, and bone-resorption capability induced by the conditioned medium from 5 G PEMF-exposed osteocytes was significantly attenuated after abrogating primary cilia in osteocytes using the polaris siRNA transfection. Together, our findings highlight that PEMF with 5 G can inhibit cellular apoptosis, modulate cytoskeletal distribution, and decrease RANKL/OPG expression in osteocytes, and also inhibit osteocyte-mediated osteoclastogenesis, which requires the existence of primary cilia in osteocytes. This study enriches our basic knowledge for further understanding the biological behaviors of osteocytes and is also helpful for providing a more comprehensive mechanistic understanding of the effect of electromagnetic stimulation on bone and relevant skeletal diseases (e.g., bone fracture and osteoporosis).