Li Xuqing, Li Jianhua, Ji Zhongyin, Li Changsheng, Wu Tao, Song Haixin, Yang Xiaotian
Department of Rehabilitation Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FASEB J. 2025 May 31;39(10):e70652. doi: 10.1096/fj.202401959RR.
Chondrocyte necroptosis contributes to the pathogenesis of osteoarthritis (OA). Pulsed electromagnetic field (PEMF) is a potentially useful treatment for OA. Here, magnetic nanoparticles and PEMF generate magneto-mechanical forces for regulating signaling pathways, but their effectiveness remains unclear. This study investigated whether magnetic nanoparticles (MIL-101(Fe)) combined with PEMF alleviate chondrocyte necroptosis in OA. Destabilization of the medial meniscus (DMM) surgery was performed to induce OA in 10-week-old wild-type mice. MIL-101(Fe) and PEMF were applied in human OA chondrocytes and experimental OA mice. Characterization and biocompatibility of MIL-101(Fe) were examined. Chondrocyte necroptosis was analyzed by western blotting, immunofluorescence, TUNEL, and transmission electron microscopy. OA severity was assessed by RT-PCR, immunofluorescence, histology, and micro-CT. We found that MIL-101(Fe) had no obvious cytotoxicity and presented biocompatibility. The combination of MIL-101(Fe) and PEMF ameliorated cartilage metabolism. PEMF attenuated cartilage degeneration and trabecular bone microarchitecture; these protective effects were enhanced by MIL-101(Fe). Further, the combination therapy markedly inhibited chondrocyte necroptosis and significantly decreased phosphorylation of RIP1, RIP3, and MLKL. Together, our findings indicate that MIL-101(Fe) combined with PEMF synergistically ameliorates chondrocyte necroptosis and OA progression without severe side effects, suggesting that this combination therapy may offer a novel strategy for treating OA.
软骨细胞坏死性凋亡参与骨关节炎（OA）的发病机制。脉冲电磁场（PEMF）是一种对OA可能有用的治疗方法。在此，磁性纳米颗粒和PEMF产生磁机械力以调节信号通路，但其有效性仍不明确。本研究调查了磁性纳米颗粒（MIL-101(Fe)）联合PEMF是否能减轻OA中软骨细胞的坏死性凋亡。对10周龄野生型小鼠进行内侧半月板不稳定（DMM）手术以诱导OA。将MIL-101(Fe)和PEMF应用于人类OA软骨细胞和实验性OA小鼠。检测了MIL-101(Fe)的特性和生物相容性。通过蛋白质免疫印迹、免疫荧光、TUNEL和透射电子显微镜分析软骨细胞坏死性凋亡。通过RT-PCR、免疫荧光、组织学和微型计算机断层扫描评估OA严重程度。我们发现MIL-101(Fe)没有明显的细胞毒性且具有生物相容性。MIL-101(Fe)与PEMF的联合改善了软骨代谢。PEMF减轻了软骨退变和小梁骨微结构；MIL-101(Fe)增强了这些保护作用。此外，联合治疗显著抑制了软骨细胞坏死性凋亡，并显著降低了RIP1、RIP3和MLKL的磷酸化。总之，我们的研究结果表明，MIL-101(Fe)联合PEMF可协同减轻软骨细胞坏死性凋亡和OA进展，且无严重副作用，提示这种联合治疗可能为OA治疗提供一种新策略。
