<b>Regulation of mouse chondrocyte differentiation by CCAAT/enhancer-binding pr</b><b>oteins </b>

DOI PubMed 1 Citations 39 References
  • OKUMA Tomotake
    Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo
  • HIRATA Makoto
    Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo
  • YANO Fumiko
    Bone and Cartilage Regenerative Medicine, Faculty of Medicine, University of Tokyo Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo
  • MORI Daisuke
    Bone and Cartilage Regenerative Medicine, Faculty of Medicine, University of Tokyo
  • KAWAGUCHI Hiroshi
    Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo Spine Center, Tokyo Shinjuku Medical Center, Japan Community Health care Organization
  • CHUNG Ung-il
    Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo
  • TANAKA Sakae
    Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo
  • SAITO Taku
    Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo Bone and Cartilage Regenerative Medicine, Faculty of Medicine, University of Tokyo

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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.

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