Regulation of mouse chondrocyte differentiation by CCAAT/enhancer-binding proteins
Abstract
CCAAT/enhancer-binding protein (C/EBP) β regulates chondrocyte differentiaion and proliferation during endochondral ossification. However, expression and function of other C/EBP family members in chondrocytes have not been fully understood. To understand the comprehensive regulation of chondrocyte differentiation by C/EBPs, we initially examined their expression levels. Among four members (C/EBPα, C/EBPβ, C/EBPδ and C/EBPε) with transactivation domain, expression of Cebpb and Cebpd was abundant compared to Cebpa, while Cebpe was hardly expressed in mouse isolated chondrocytes. Doxycycline (DOX)-inducible overexpression of each of the three C/EBPs (C/EBPα, C/EBPβ and C/EBPδ) in ATDC5 cells suppressed expressions of early differentiation markers including Col2a1, aggrecan and Sox9, enhanced those of late differentiation markers including Mmp13, Vegfa and Col10a1, and decelerated cell proliferation, indicating their overlapped functions in chondrocytes. In contrast, DOX-inducible overexpression of A-CEBP, which exerts a dominant-negative effect against all C/EBPs, increased expressions of early differentiation markers and decreased those of late differentiation markers. Finally, microarray and gene ontology analyses showed that A-...Continue Reading
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