Investigation on the role of FGF-1 in CCN2 gene regulation and osteoarthritis

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FGF-1 strongly inhibits the gene expression of CCN2, which regenerates cartilage, whereas it enhances its own gene expression in chondrocytes. This effect is thought to be critical in osteoarthritis development mediated by FGF-1. In order to find out an intracellular factor that mediate this gene regulation, I initially analyzed chromatin immunoprecipitation (ChIP) sequencing data downloaded from the ENCODE database. According to the ChIP data, both CCN2 and FGF-1 genes contains 2 regions accompanied by H3K4me2, which is a hallmark of promoter, enhancer and silencer, in the proximal promoter area. Interestingly, I found a transcription factor that binds to one of these 2 regions of both genes. Gene expression of this transcription factor was confirmed in human chondrocytic cells. After silencing the expression of this factor in those cells by siRNAs, I evaluated the effect of FGF-1 on the CCN2 and FGF-1 genes. As expected, FGF-1 failed to regulate the CCN2 and FGF-1 genes after the silencing of the transcription factor gene. These results indicate that this single transcription factor mediates both CCN2 repression and auto-induction by FGF-1. Utility of a molecule that inhibits the function of this transcription factor in osteoarthritis treatment is suggested herein.