Author: Kangping Song1,2,3, Jing Hu1,2,3, Ming Yang4, Yong Xia1,2,3, Chengqi He1,2,3, Yonghong Yang5,6,7, Siyi Zhu8,9,10
Affiliation: <sup>1</sup> Rehabilitation Medicine Center, Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, #37 Guoxue Alley, Wuhou strict, Chengdu, Sichuan, 610041, PR China.
<sup>2</sup> Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, China.
<sup>3</sup> School of Rehabilitation Sciences, West China School of Medicine, Sichuan University, Chengdu, China.
<sup>4</sup> The Lab of Aging Research, State Key Laboratory of Biotherapy, West China Hospital, National Clinical Research Center for Geriatrics, Sichuan University, Chengdu, China.
<sup>5</sup> Rehabilitation Medicine Center, Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, #37 Guoxue Alley, Wuhou strict, Chengdu, Sichuan, 610041, PR China. nicole308@126.com.
<sup>6</sup> Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, China. nicole308@126.com.
<sup>7</sup> School of Rehabilitation Sciences, West China School of Medicine, Sichuan University, Chengdu, China. nicole308@126.com.
<sup>8</sup> Rehabilitation Medicine Center, Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, #37 Guoxue Alley, Wuhou strict, Chengdu, Sichuan, 610041, PR China. hxkfzsy@scu.edu.cn.
<sup>9</sup> Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, China. hxkfzsy@scu.edu.cn.
<sup>10</sup> School of Rehabilitation Sciences, West China School of Medicine, Sichuan University, Chengdu, China. hxkfzsy@scu.edu.cn.
Conference/Journal: J Transl Med
Date published: 2024 Aug 6
Other:
Volume ID: 22 , Issue ID: 1 , Pages: 741 , Special Notes: doi: 10.1186/s12967-024-05470-7. , Word Count: 266
Background:
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).
Purpose:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Keywords: Mesenchymal stem cells; Osteoarthritis; Pulsed electromagnetic fields.
PMID: 39107784 PMCID: PMC11301989 DOI: 10.1186/s12967-024-05470-7