tailieunhanh - Báo cáo khoa học: The cartilage-specific transcription factor Sox9 regulates AP-2e expression in chondrocytes

Activating enhancer-binding protein (AP)-2ewas previously described as a new regulator of integrina10 expression in cartilage. In this study, we ana-lyzed the expression of AP-2ein differentiated chondrocytes and in human mesenchymal stem cells (HMSCs), which have been differentiated into chondrocytes in vitro. | The cartilage-specific transcription factor Sox9 regulates AP-2e expression in chondrocytes Ann-Kathrin Wenke1 Susanne Grassel2 Markus Moser3 and Anja K. Bosserhoff1 1 Institute of Pathology University Regensburg Germany 2 Department of Orthopedics University Regensburg Germany 3 Max-Planck-Institute of Biochemistry Martinsried Germany Keywords AP-2e cartilage differentiation osteoarthritis transcriptional regulation Correspondence . Bosserhoff Institute of Pathology University of Regensburg Franz-Josef-Strauss-Allee 11 D-93053 Regensburg Germany Fax 49 941 944 6602 Tel 49 941 944 6705 E-mail . Received 14 January 2009 revised 13 February 2009 accepted 18 February 2009 doi Activating enhancer-binding protein AP -2e was previously described as a new regulator of integrin a10 expression in cartilage. In this study we analyzed the expression of AP-2e in differentiated chondrocytes and in human mesenchymal stem cells HMSCs which have been differentiated into chondrocytes in vitro. AP-2e is predominantly expressed during the late stages of chondrocyte differentiation mainly in early hypertrophic cartilage consistent with immunohistochemical stainings of mouse embryo sections. Furthermore osteoarthritic chondrocytes resembling a hypertrophic phenotype have high AP-2e levels. The AP-2e promoter harbors binding sites for the transcription factors AP-2a and Sox9. Both transcription factors strongly activate AP-2e expression in a cooperative manner in the chondrosarcoma cell line SW1353. The inhibition of Sox9 expression by small interfering RNA resulted in decreased AP-2e expression. In addition direct interaction of Sox9 with the AP-2e promoter could be confirmed by chromatin immunoprecipitation and electromobility shift assays. This is the first study to prove the direct regulation of AP-2e by the transcription factor Sox9 and to indicate that AP-2e potentially has an important role as a .