Low-Intensity Pulsed Ultrasound Activates Integrin-Mediated Mechanotransduction Pathway in Synovial Cells

Low-intensity pulsed ultrasound (LIPUS) suppresses synovial hyperplasia and synovial cell proliferation characterized for rheumatoid arthritis, but the molecular mechanisms remain unknown. The purpose of this study was to examine the mechanotransduction pathway via the integrin/mitogen-activated protein kinase (MAPK) pathway in LIPUS exposure on the synovial membrane cells. Rabbit knee synovial membrane cell line, HIG-82, was cultured with or without FAK phosphorylation inhibitor, PF-573228. One hour after stimulation with PF-573228, the cells exposed to LIPUS for 20 min or sham exposure. A possible integrin/MAPK pathway was examined by immunofluorescence and Western blotting analysis with antibodies targeting specific phosphorylation sites on intracellular signaling proteins. LIPUS exposure increased phosphorylation of FAK, JNK, ERK, and p38, but the phosphorylation was inhibited by PF-573228. In conclusion, LIPUS exposure might be involved in cell apoptosis and survival of synovial membrane cells via integrin/FAK/MAPK pathway.