First Author | Wenke AK | Year | 2009 |
Journal | FEBS J | Volume | 276 |
Issue | 9 | Pages | 2494-504 |
PubMed ID | 19476490 | Mgi Jnum | J:149665 |
Mgi Id | MGI:3848843 | Doi | 10.1111/j.1742-4658.2009.06973.x |
Citation | Wenke AK, et al. (2009) The cartilage-specific transcription factor Sox9 regulates AP-2epsilon expression in chondrocytes. FEBS J 276(9):2494-504 |
abstractText | Activating enhancer-binding protein (AP)-2epsilon was previously described as a new regulator of integrin alpha(10) expression in cartilage. In this study, we analyzed the expression of AP-2epsilon in differentiated chondrocytes and in human mesenchymal stem cells (HMSCs), which have been differentiated into chondrocytes in vitro. AP-2epsilon 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-2epsilon levels. The AP-2epsilon promoter harbors binding sites for the transcription factors AP-2alpha and Sox9. Both transcription factors strongly activate AP-2epsilon expression in a cooperative manner in the chondrosarcoma cell line SW1353. The inhibition of Sox9 expression by small interfering RNA resulted in decreased AP-2epsilon expression. In addition, direct interaction of Sox9 with the AP-2epsilon promoter could be confirmed by chromatin immunoprecipitation and electromobility shift assays. This is the first study to prove the direct regulation of AP-2epsilon by the transcription factor Sox9, and to indicate that AP-2epsilon potentially has an important role as a modulator of hypertrophic cartilage. |