Reference - Detail
|Author||Okuma T, Hirata M, Yano F, Mori D, Kawaguchi H, Chung UI, Tanaka S, Saito T.|
|Title||Regulation of mouse chondrocyte differentiation by CCAAT/enhancer-binding proteins.|
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-CEBP altered many genes related with various events or tissues such as skeletal development, cartilage, cell cycle, inflammation and apoptosis. In conclusion, C/EBPα, C/EBPβ and C/EBPδ regulate proliferation and differentiation of chondrocytes and possibly is involved with apoptosis and inflammation. C/EBPs may play a variety of roles in the homeostasis of joint cartilage under physiological and pathological conditions.
|MeSH||Aggrecans / genetics Aggrecans / metabolism Animals Apoptosis / drug effects Apoptosis / genetics CCAAT-Enhancer-Binding Protein-beta / genetics CCAAT-Enhancer-Binding Protein-beta / metabolism* CCAAT-Enhancer-Binding Protein-delta / genetics CCAAT-Enhancer-Binding Protein-delta / metabolism* CCAAT-Enhancer-Binding Proteins / genetics CCAAT-Enhancer-Binding Proteins / metabolism* Cartilage / cytology Cartilage / drug effects Cartilage / growth & development Cartilage / metabolism* Cell Cycle / drug effects Cell Differentiation / drug effects Cell Proliferation / drug effects Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / metabolism* Collagen Type II / genetics Collagen Type II / metabolism Collagen Type X / genetics Collagen Type X / metabolism Doxycycline / pharmacology Gene Expression Regulation, Developmental* Matrix Metalloproteinase 13 / genetics Matrix Metalloproteinase 13 / metabolism Mice Mice, Inbred C57BL Plasmids / chemistry Plasmids / metabolism Primary Cell Culture SOX9 Transcription Factor / genetics SOX9 Transcription Factor / metabolism Signal Transduction Transformation, Genetic Vascular Endothelial Growth Factor A / genetics Vascular Endothelial Growth Factor A / metabolism|
|WOS Category||MEDICINE, RESEARCH & EXPERIMENTAL|
|Human and Animal Cells|