Huang Jinming, Li Yi, Zhu Siyi, Wang Liqiong, Pei Hongliang, Wang Xiangxiu, Bao Tianjie, Jiang Zhiyuan, Yang Lin, He Chengqi
Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Key Laboratory of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
J Tissue Eng Regen Med. 2023 Jun 3;2023:8857436. doi: 10.1155/2023/8857436. eCollection 2023.
Insufficient bone formation is the key reason for the imbalance of bone metabolism and one of the main mechanisms for the occurrence and deterioration of postmenopausal osteoporosis (PMOP). Accumulating evidence has demonstrated that pulsed electromagnetic field (PEMF), as a physiotherapy, can treat osteoporosis by promoting osteogenic differentiation in osteoblasts. However, little is known about its mechanisms.
, ovariectomized mice were administered PEMF for 4 weeks, and skeletal analysis was conducted. , hydrogen peroxide-treated mouse osteoblast precursor cells with or without PEMF intervention were subjected to osteogenic differentiation testing and miRNA microarrays. The potential target miRNAs were validated, followed by gene expression assays to further clarify their regulatory relationships with target pathways.
We found that PEMF reduced bone loss in ovariectomized mice and promoted osteogenic differentiation of hydrogen peroxide-treated osteoblast precursor cells via downregulation of miR-6976-5p. Mechanistically, reduced miR-6976-5p enhanced the nuclear transport of phosphorylated Smad1/5/9 by upregulating Smad4, thereby activating the BMP/Smad pathway. Additionally, the administration of miR-6976-5p inhibitors successfully promoted osteogenic differentiation in vitro, and its antagomirs protected bone mass in vivo. miR-6976-5p mimics and agomirs acted in the opposite way.
These results provide evidence that PEMF alleviates estrogen deficiency-induced bone loss by activating osteoblastic progenitor cells and maintaining their osteogenic differentiation and shed light on the mechanisms involved, which may provide a potential option for the clinical application of PEMF in PMOP.
骨形成不足是骨代谢失衡的关键原因，也是绝经后骨质疏松症（PMOP）发生和恶化的主要机制之一。越来越多的证据表明，脉冲电磁场（PEMF）作为一种物理疗法，可通过促进成骨细胞的成骨分化来治疗骨质疏松症。然而，其作用机制尚不清楚。
对去卵巢小鼠进行4周的PEMF治疗，并进行骨骼分析。对过氧化氢处理的小鼠成骨细胞前体细胞进行PEMF干预或不干预，然后进行成骨分化测试和miRNA微阵列分析。验证潜在的靶miRNA，随后进行基因表达分析，以进一步阐明它们与靶途径的调控关系。
我们发现，PEMF通过下调miR-6976-5p减少去卵巢小鼠的骨质流失，并促进过氧化氢处理的成骨细胞前体细胞的成骨分化。机制上，miR-6976-5p的减少通过上调Smad4增强了磷酸化Smad1/5/9的核转运，从而激活BMP/Smad途径。此外，给予miR-6976-5p抑制剂成功促进了体外成骨分化，其拮抗剂在体内保护了骨量。miR-6976-5p模拟物和激动剂的作用则相反。
这些结果提供了证据，表明PEMF通过激活成骨祖细胞并维持其成骨分化来减轻雌激素缺乏引起的骨质流失，并揭示了其中涉及的机制，这可能为PEMF在PMOP中的临床应用提供一个潜在的选择。
