CXCL1, 2, and 3 Expression Stimulated by Fibronectin Fragments in Synovial Fibroblasts from Human Temporomandibular Joints

Abstract

　Fibronectin, which is an extracellular matrix component, is broken down by several matrix degradation enzymes. Fibronectin-fragments (FN-fs), with molecular sizes of 29-200 kDa, are present at high levels in synovial fluid from osteoarthritis patients. The roles of FN-fs in temporomandibular joint (TMJ) arthritides were investigated. The 120 kDa FN-f was the most potent inducer of the expression and production of CXCL1, also called growth-related oncogene α (GROα), compared to 30 kDa and 45 kDa FN-fs in synovial fibroblasts (SF) from human temporomandibular joints. Therefore, further investigation was carried out using the 120 kDa FN-f. Microarray analysis indicated that 120 kDa FN-f treatment of SF upregulated the expressions of CXCL1 and chemokines. Real-time PCR analysis showed that the gene expressions of CXCL1, CXCL2, and CXCL3 were significantly higher in 120 kDa FN-f-treated SF than in untreated controls. CXCL1 protein production was increased by the 120 kDa FN-f in a time-dependent manner. Furthermore, signal inhibitor experiments indicated that 120 kDa FN-f-mediated induction of CXCL1 was transduced via activation of NFκB signaling. These results suggest that the 120 kDa FN-f is associated with the inflammatory progression of TMJ arthritides.