Pulsed electromagnetic field attenuates senescence-associated cartilage degradation in aging mice via the Nrf2/HO-1 signaling pathway

Pulsed electromagnetic field (PEMF) possesses anti-oxidative and anti-inflammatory properties. However, its role in chondrocyte senescence and age-related osteoarthritis (OA) remains poorly understood. This study aimed to investigate the potential protective effects of PEMF against age-related cartilage degradation. Chondrocytes (C28/I2) were treated with D-galactose (D-gal) and subsequently exposed to PEMF. In vitro, cell viability, chondrocyte senescence, extracellular matrix (ECM) degradation, oxidative stress, and mitochondrial function were assessed. Additionally, RNA sequencing and a NF-E2-related factor 2 (Nrf2) inhibitor ML385 were employed to identify and validate potential signaling pathways modulated by PEMF. Furthermore, in an aging murine model induced by D-gal, histological staining was performed to evaluate the protective effects of PEMF against cartilage degradation. PEMF promotes chondrocytes proliferation under D-gal treatment and effectively regulate the senescence phenotype induced by D-gal. Additionally, PEMF improves the metabolic balance of the ECM. RNA-seq analyses indicate that PEMF exerts its effect on D-gal-treated chondrocytes through the inhibition of oxidative stress-mediated cellular senescence. Subsequently, the reduced ROS levels, enhanced mitochondrial membrane potential, and more comprehensive mitochondrial morphology collectively demonstrated the anti-oxidative stress capacity of PEMF in senescent chondrocytes. The use of Nrf2 inhibitor ML385 weakens the above effects of PEMF. Then, PEMF exposure was shown to significantly suppress the nuclear translocation of p65 and the degradation of IκB-α, while concurrently enhancing the expression levels of Nrf2 and heme oxygenase-1 (HO-1) in senescent chondrocytes. Finally, histological and immunofluorescent analyses demonstrated that aging mice subjected to PEMF treatment exhibited milder cartilage degradation and a reduced number of senescent chondrocytes in the joints compared to untreated aging controls. Our study demonstrated that PEMF attenuates chondrocyte senescence and cartilage degradation through regulation of the Nrf2/HO-1 signaling pathway, thereby elucidating its underlying mechanism and therapeutic potential in age-related OA.