GAS5 long non-coding RNA interacts with microRNA-205 to relieve fibroblast-like synoviocyte inflammation and ferroptosis in osteoarthritis.

Abstract

This study aimed to explore the role of the growth arrest-specific five gene (GAS5) long non-coding RNA (lncRNA) in fibroblast-like synoviocytes (FLSs) during the development of osteoarthritis (OA). A total of 25 OA synovial tissues and nine healthy control tissues were collected, and their GAS5 expression was compared. To confirm GAS5 expression in vitro, interleukin (IL)-1β was used to mimic a cellular OA model based on isolated FLSs. Quantitative polymerase chain reaction revealed higher expression levels of GAS5 in OA samples than in non-OA samples. In vitro, the stimulation of FLSs by IL-1β induced high GAS5 expression. The IL-1β-exposed cells exhibited impaired growth, viability, and antioxidant capacity, as well as increased cell death, production of cellular and lipid ROS, and inflammatory cytokine levels. The expression levels of ferroptosis-related proteins in FLSs were also altered in IL-1β-exposed cells. GAS5 was observed to directly target and inhibit micro-RNA 205, partially reversing the effect of GAS5 silencing on cell proliferation, cell death, oxidative stress, inflammation, and FLS ferroptosis. FLS ferroptosis is recognized to be involved in OA development, and the downregulation of the GAS5 lncRNA exhibits protective effects by suppressing ferroptosis and sponging miR-205 in FLSs in OA, thereby providing a novel strategy for the treatment of OA. The GAS5-miR-205 axis can regulate inflammation and oxidative stress in the FLSs of patients with OA.