抄録
Tumor necrosis factor-α(TNF-α) plays a key role in pathological conditions of the temporomandibular joint (TMJ). However, the molecular mechanisms by which TNF-α contributes to synovial inflammation remain unclear. In this study, the gene expression profile of synovial fibroblasts stimulated by TNF-α was studied by Gene Chip analysis. Synovial fibroblasts were prepared from the tissues of three patients with internal derangement of the TMJ, using the outgrowth method. The synovial cells were stimulated by TNF-α for 4 hours, after which total RNA was extracted with TRlzol. Gene expression profiling was performed using the Affymetrix Gene Chip (Human Genome Focus Array, 8500 genes). Hybridization data were analyzed with Gene Spring software.
Two hundred forty-five genes were found to be TNF-α responsive, showing a greater than two-fold difference in average intensity between the stimulated and control samples. The gene ontology classification was the “transregulator”, “catalytic activity”, “transcription regulator”, and “chaperone activity” categories. Among the top 25 up-regulated genes, 8 were found to be chemokines. The expression of chemokines in TNF-α responsive genes measured by Gene Chip was confirmed by real time-PCR. Chemokine gene expression was found to be increased by TNF-α.
These results suggest that TNF-α may contribute to inflammation in internal derangement of the TMJ by producing chemokines.
