| First Author | Park NR | Year | 2016 |
| Journal | J Cell Physiol | Volume | 231 |
| Issue | 1 | Pages | 162-71 |
| PubMed ID | 26058470 | Mgi Jnum | J:309481 |
| Mgi Id | MGI:6757362 | Doi | 10.1002/jcp.25068 |
| Citation | Park NR, et al. (2016) Core Binding Factor beta Plays a Critical Role During Chondrocyte Differentiation. J Cell Physiol 231(1):162-71 |
| abstractText | Core binding factor beta (Cbfbeta) is a partner protein of Runx family transcription factors with minimally characterized function in cartilage. Here we address the role of Cbfbeta in cartilage by generating chondrocyte-specific Cbfbeta-deficient mice (Cbfb(Deltach/Deltach) ) from Cbfb-floxed mice crossed with mice expressing Cre from the Col2a1 promoter. Cbfb(Deltach/Deltach) 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(Deltach/Deltach) mice compared to wild type mice. With regard to signaling pathways, both PTHrP-Ihh and BMP signaling were compromised in Cbfb(Deltach/Deltach) mice. Mechanistically, Cbfbeta 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(Deltach/Deltach) mice. Collectively, these findings indicate that Cbfbeta plays a critical role for chondrocyte differentiation through stabilizing Runx2 and Runx3 proteins in cartilage. |
