Downregulation of Gadd45β alleviates osteoarthritis by repressing lipopolysaccharide-induced fibroblast-like synoviocyte inflammation, proliferation and migration.

OBJECTIVE:Gadd45β have a regulatory role in cellular inflammation, proliferation and migration. However, the role of Gadd45β in synovial inflammation in osteoarthritis (OA) remains to be explored. This study aimed to ascertain whether Gadd45β is involved in OA synovial inflammation. METHODS:The rat model was induced by sodium iodoacetate and the cellular model was constructed with lipopolysaccharide (LPS)-induced fibroblast-like synoviocytes (FLSs). siRNA was applied to interfere with the expression of intracellular Gadd45β. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of Gadd45β mRNA and protein. The inflammation, proliferation, and migration of OA-FLSs were detected by enzyme-linked immunosorbent assay, cell scratch assay, 5-ethynyl-2'-deoxyuridine assay, etc. The effect of downregulation of Gadd45β on the nuclear factor-κB (NF-κB) pathway was investigated. RESULTS:Expression of Gadd45β in OA rat synovial tissues and OA-FLSs was increased, and LPS treatment promoted cell proliferation and enhanced cell migration. Gadd45β interference inhibited the inflammation, proliferation and migration of cells induced by LPS. LPS promoted P65 expression in the nucleus and activated the NF-κB signaling pathway, whereas si-Gadd45β reversed this situation. CONCLUSIONS:si-Gadd45β inhibited the inflammatory response, proliferation and migration of FLSs, and activation of the NF-κB signaling pathway, which could delay the progression of OA. Hence, it may become a potential therapeutic target for OA.