The cartilage-specific transcription factor Sox9 regulates AP-2 epsilon expression in chondrocytes

Wenke, Ann-Kathrin and Grassel, Susanne and Moser, Markus and Bosserhoff, Anja K. (2009) The cartilage-specific transcription factor Sox9 regulates AP-2 epsilon expression in chondrocytes. FEBS JOURNAL, 276 (9). pp. 2494-2504. ISSN 1742-464X, 1742-4658

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Abstract

Activating enhancer-binding protein (AP)-2 epsilon was previously described as a new regulator of integrin alpha(10) expression in cartilage. In this study, we analyzed the expression of AP-2 epsilon in differentiated chondrocytes and in human mesenchymal stem cells (HMSCs), which have been differentiated into chondrocytes in vitro. AP-2 epsilon 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-2 epsilon levels. The AP-2 epsilon promoter harbors binding sites for the transcription factors AP-2 alpha and Sox9. Both transcription factors strongly activate AP-2 epsilon expression in a cooperative manner in the chondrosarcoma cell line SW1353. The inhibition of Sox9 expression by small interfering RNA resulted in decreased AP-2 epsilon expression. In addition, direct interaction of Sox9 with the AP-2 epsilon promoter could be confirmed by chromatin immunoprecipitation and electromobility shift assays. This is the first study to prove the direct regulation of AP-2 epsilon by the transcription factor Sox9, and to indicate that AP-2 epsilon potentially has an important role as a modulator of hypertrophic cartilage.

Item Type: Article
Uncontrolled Keywords: GROWTH-PLATE CHONDROCYTES; COLLAGEN GENE-EXPRESSION; FACTOR AP-2; DNA-BINDING; MALIGNANT-MELANOMA; RETINOIC ACID; II COLLAGEN; LIMB-BUD; DIFFERENTIATION; CHONDROGENESIS; AP-2 epsilon; cartilage; differentiation; osteoarthritis; transcriptional regulation
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Orthopädie
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 16 Sep 2020 10:31
Last Modified: 01 Dec 2020 12:13
URI: https://pred.uni-regensburg.de/id/eprint/29042

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