OBJECTIVESTemporomandibular joint (TMJ) osteoarthritis (OA) is an inflammatory disease that involves periarthritis of the TMJ and destruction of cartilage tissue in the mandibular condyle. However, the role of proinflammatory cytokines in the expression levels of matrix metalloproteinase (MMP) remains inconclusive. Thus, in this study, we aimed to investigate the effect of proinflammatory cytokines on the expression of MMPs.METHODSFLS1 cells (mouse TMJ-derived synovial cell line) were treated with tumor necrosis factor alpha (TNF-α) or interleukin (IL)-1β in the presence or absence of mitogen-activated protein kinase (MAPK) inhibitors. The mRNA expression levels of MMP-2 and MMP-9 were examined by reverse transcription-quantitative polymerase chain reaction. Additionally, the phosphorylation status of extracellular signal-regulated kinase (ERK)1/2 and p38 MAPK in the FLS1 cells treated with TNF-α or IL-1β was evaluated by performing western blotting analysis.RESULTSTNF-α and IL-1β significantly increased the expression of MMP-9 in the FLS1 cells; however, MMP-2 expression remained unaffected. Mitogen-activated protein kinase kinase (MEK) and p38 MAPK inhibitors significantly suppressed cytokine-induced MMP-9 upregulation. Conversely, Jun amino-terminal kinase (JNK) inhibitors further increased MMP-9 expression in the cells treated with TNF-α or IL-1β. Moreover, TNF-α and IL-1β enhanced ERK1/2 and p38 MAPK phosphorylation in the FLS1 cells.CONCLUSIONSTNF-α and IL-1β induced MMP-9 expression in the FLS1 cells via the MEK/ERK and p38 MAPK pathways and suppressed it via the JNK pathway. Thus, proinflammatory cytokines control MMP-9 expression in TMJ-OA by regulating multiple MAPK pathways.