Rehabilitation Medicine Center, Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, #37 Guoxue Alley, Wuhou strict, Chengdu, Sichuan, 610041, PR China.
Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, China.
J Transl Med. 2024 Aug 6;22(1):741. doi: 10.1186/s12967-024-05470-7.
Pulsed electromagnetic fields (PEMFs) show promise as a treatment for knee osteoarthritis (KOA) by reducing inflammation and promoting chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs).
To identify the efficacy window of PEMFs to induce BMSCs chondrogenic differentiation and explore the cellular mechanism under chondrogenesis of BMSCs in regular and inflammatory microenvironments.
BMSCs were exposed to PEMFs (75 Hz, 1.6/2/3/3.8 mT) for 7 and 14 days. The histology, proliferation, migration and chondrogenesis of BMSCs were assessed to identify the optimal parameters. Using these optimal parameters, transcriptome analysis was performed to identify target genes and signaling pathways, validated through immunohistochemical assays, western blotting, and qRT-PCR, with or without the presence of IL-1β. The therapeutic effects of PEMFs and the effective cellular signaling pathways were evaluated in vivo.
BMSCs treated with 3 mT PEMFs showed the optimal chondrogenesis on day 7, indicated by increased expression of ACAN, COL2A, and SOX9, and decreased levels of MMP3 and MMP13 at both transcriptional and protein levels. The advantages of 3 mT PEMFs diminished in the 14-day culture groups. Transcriptome analysis identified sFRP3 as a key molecule targeted by PEMF treatment, which competitively inhibited Wnt/β-catenin signaling, regardless of IL-1β presence or duration of exposure. This inhibition of the Wnt/β-catenin pathway was also confirmed in a KOA mouse model following PEMF exposure.
PEMFs at 75 Hz and 3 mT are optimal in inducing early-stage chondrogenic differentiation of BMSCs. The induction and chondroprotective effects of PEMFs are mediated by sFRP3 and Wnt/β-catenin signaling, irrespective of inflammatory conditions.
脉冲电磁场（PEMFs）通过减少炎症和促进骨髓间充质干细胞（BMSCs）的软骨分化，显示出治疗膝骨关节炎（KOA）的潜力。
确定 PEMFs 诱导 BMSCs 软骨分化的疗效窗口，并在常规和炎症微环境下探索 BMSCs 软骨形成过程中的细胞机制。
将 BMSCs 暴露于 PEMFs（75 Hz，1.6/2/3/3.8 mT）7 和 14 天。评估 BMSCs 的组织学、增殖、迁移和软骨分化，以确定最佳参数。使用这些最佳参数进行转录组分析，以鉴定靶基因和信号通路，通过免疫组织化学检测、Western blot 和 qRT-PCR 进行验证，同时存在或不存在 IL-1β。在体内评估 PEMFs 的治疗效果和有效细胞信号通路。
3 mT PEMFs 处理的 BMSCs 在第 7 天表现出最佳的软骨形成，表现为 ACAN、COL2A 和 SOX9 的表达增加，以及 MMP3 和 MMP13 的转录和蛋白水平降低。在 14 天培养组中，3 mT PEMFs 的优势减弱。转录组分析确定 sFRP3 是 PEMF 治疗的关键靶分子，它竞争性抑制 Wnt/β-catenin 信号通路，无论 IL-1β的存在与否或暴露时间长短。这种 Wnt/β-catenin 通路的抑制也在 PEMF 暴露后的 KOA 小鼠模型中得到了证实。
75 Hz 和 3 mT 的 PEMFs 是诱导 BMSCs 早期软骨分化的最佳选择。PEMFs 的诱导和软骨保护作用是由 sFRP3 和 Wnt/β-catenin 信号通路介导的，与炎症状态无关。
