Low-intensity pulsed ultrasound inhibits chondrocyte senescence by inhibiting PI3K/AKT/mTOR signaling.

Abstract

Cellular senescence is an important cause of age-related degenerative diseases, including osteoarthritis (OA). Chondrocyte senescence is crucial in OA onset and progression. As a non-invasive, safe, and widely used physical rehabilitation factor, the effect and mechanism of low intensity pulsed ultrasound (LIPUS) on chondrocyte senescence remain unclear. This study evaluated the inhibitory effect of LIPUS on OA chondrocyte senescence in vitro and in vivo. The effect of LIPUS on chondrocyte senescence was examined by RT-qPCR, enzyme-linked immunosorbent assay (ELISA), and western blotting. Changes in levels of reactive oxygen species (ROS) and γ-h2ax foci in senescent chondrocytes were detected using fluorescent staining. Chondrocyte senescence was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining. The PI3K inhibitor LY294002 and the PI3K agonist 740Y-P were used to investigate whether PI3K/AKT/mTOR signalling was involved in the effect of LIPUS in senescent chondrocytes. Chondrocyte senescence and cartilage degeneration were analyzed in a destabilization of the medial meniscal (DMM) mouse model by immunohistochemistry, hematoxylin and eosin staining, and safranin-O/fast green staining. LIPUS inhibited the expression of the senescence-associated secretory phenotype (SASP) factors CCL4 and CCL2 and the senescence phenotype in doxorubicin-treated chondrocytes by inhibiting the PI3K/AKT/mTOR pathway. LIPUS alleviated chondrocyte senescence and attenuated OA progression in the DMM mice. These results demonstrated a novel role for LIPUS in inhibiting chondrocyte senescence and the SASP by modulating PI3K/AKT/mTOR signalling. Our findings expanded the clinical application of LIPUS and provide a new, non-invasive, and safe treatment approach to prevent and treat age-related degenerative joint disorders.