title: Core Binding Factor β Plays a Critical Role During Chondrocyte Differentiation.
abstract: Core binding factor β (Cbfβ) is a partner protein of Runx family transcription factors with minimally characterized function in cartilage. Here we address the role of Cbfβ in cartilage by generating chondrocyte-specific Cbfβ-deficient mice (Cbfb(Δch/Δch) ) from Cbfb-floxed mice crossed with mice expressing Cre from the Col2a1 promoter. Cbfb(Δch/Δch) mice died soon after birth and exhibited delayed endochondral bone formation, shorter appendicular skeleton length with increased proliferative chondrocytes, and nearly absent hypertrophic chondrocyte zones. Immunohistochemical and quantitative real-time PCR analyses showed that the number and size of proliferative chondrocytes increased and the expression of chondrocyte maturation markers at the growth plates, including Runx2, osterix, and osteopontin, significantly diminished in Cbfb(Δch/Δch) mice compared to wild type mice. With regard to signaling pathways, both PTHrP-Ihh and BMP signaling were compromised in Cbfb(Δch/Δch) mice. Mechanistically, Cbfβ deficiency in chondrocytes caused a decrease of protein levels of Runx transcription factors by accelerating polyubiquitination-mediated proteosomal degradation in vitro. Indeed, Runx2 and Runx3, but not Runx1, decreased in Cbfb(Δch/Δch) mice. Collectively, these findings indicate that Cbfβ plays a critical role for chondrocyte differentiation through stabilizing Runx2 and Runx3 proteins in cartilage.
authors.affiliation: Department of Biochemistry and Cell Biology, Skeletal Diseases Genome Research Center, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Na-Rae
authors.initials: NR
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Cell Biology, Skeletal Diseases Genome Research Center, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Kyung-Eun
authors.initials: KE
authors.lastname: Lim
authors.affiliation: Department of Biochemistry and Cell Biology, Skeletal Diseases Genome Research Center, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Min-Su
authors.initials: MS
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Cell Biology, Skeletal Diseases Genome Research Center, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Che
authors.affiliation: Department of Biochemistry and Cell Biology, Skeletal Diseases Genome Research Center, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Clara Yongjoo
authors.initials: CY
authors.lastname: Park
authors.affiliation: Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Laboratory for Transcriptional Regulation, RIKEN Research Center for Allergy and Immunology, Kanagawa, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Taniuchi
authors.affiliation: Department of Biochemistry, Institute for Tumor Research, Chungbuk National University, College of Medicine, Cheongju, Republic of Korea.
authors.forename: Suk-Chul
authors.initials: SC
authors.lastname: Bae
authors.affiliation: Department of Biochemistry and Cell Biology, Skeletal Diseases Genome Research Center, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Choi
mesh_terms: D000818:Animals; D002356:Cartilage / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics*; D019902:Chondrocytes / Q000166:cytology*; D020219:Chondrogenesis / Q000235:genetics*; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006132:Growth Plate / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010012:Osteogenesis / Q000502:physiology
chemical_list: C493693:Cbfb protein, mouse; D050658:Core Binding Factor beta Subunit