Regulation of integrin alpha10 expression in chondrocytes by the transcription factors AP-2epsilon and Ets-1.

Expression of integrin alpha10 is initiated at the beginning of chondrogenesis and continues throughout cartilage development in adult cartilage. In our study, we aim to identify regulatory sequences that control the cell-type specific expression of the human integrin alpha10 gene. Therefore, promoter constructs harboring 1139bp 5' of the transcriptional start site of the human integrin alpha10 gene were analyzed. Our experiments localized a promoter region that directs high levels of expression specifically in chondrocytes. A sequence analysis detected three consensus AP-2 binding sites within this functional domain. Functionality of these sites was tested and confirmed by cotransfection of AP-2 in a luciferase reporter assay. Interestingly, EMSA identified AP-2epsilon as the major AP-2 protein binding to the AP-2 consensus sequences. Additionally, Ets-1 was shown to be a positive regulator of the integrin alpha10 expression whereas Sox9 was irrelevant. Taken together, these results suggest that AP-2epsilon and Ets-1 are involved in the regulation of integrin alpha10 transcription in chondrocytes.