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.
Arthritis Res Ther. 2025-2-14
RSC Med Chem. 2023-9-1