Core Binding Factor β Plays a Critical Role During Chondrocyte Differentiation. Issue 1 (January 2016)

• Record Type: Journal Article
• Authors: Park, Na‐Rae; Lim, Kyung‐Eun; Han, Min‐Su; Che, Xiangguo; Park, Clara Yongjoo; Kim, Jung‐Eun; Taniuchi, Ichiro; Bae, Suk‐Chul; Choi, Je‐Yong
• Is Part Of: Journal of cellular physiology. Volume 231:Issue 1(2016:Jan.)
• Page Start: 162
• Page End: 171
• Publication Date: 2016-01
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.25068
• Languages: English
• ISSNs: 0021-9541

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jcp25068-sec-0001" sec-type="section"> <p>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 (<italic>Cbfb<sup>Δch/Δch</sup></italic>) from <italic>Cbfb</italic>‐floxed mice crossed with mice expressing Cre from the <italic>Col2a1</italic> promoter. <italic>Cbfb<sup>Δch/Δch</sup></italic> 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 <italic>Cbfb<sup>Δch/Δch</sup></italic> mice compared to wild type mice. With regard to signaling pathways, both PTHrP‐Ihh and BMP signaling were compromised in <italic>Cbfb<sup>Δch/Δch</sup></italic> 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 <italic>Cbfb<sup>Δch/Δch</sup></italic> mice. Collectively, these findings indicate that Cbfβ plays a critical role for chondrocyte differentiation through stabilizing Runx2 and Runx3 proteins in cartilage J. Cell. Physiol. 230: 162–171, 2016. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>