Magnetic Nanoparticles Combined With Pulsed Electromagnetic Field Alleviate Chondrocyte Necroptosis in Osteoarthritis.

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.