The cartilage-specific transcription factor Sox9 regulates AP-2epsilon expression in chondrocytes.
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.
Wenke
Ann-Kathrin
AK
Institute of Pathology, University Regensburg, Germany.
Grässel
Susanne
S
Moser
Markus
M
Bosserhoff
Anja K
AK
D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D055758:SOX9 Transcription Factor / Q000378:metabolism*; D050656:Transcription Factor AP-2 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D055758:SOX9 Transcription Factor; D050656:Transcription Factor AP-2