| First Author | Wu M | Year | 2014 |
| Journal | Int J Biol Sci | Volume | 10 |
| Issue | 8 | Pages | 861-72 |
| PubMed ID | 25170300 | Mgi Jnum | J:287218 |
| Mgi Id | MGI:6402995 | Doi | 10.7150/ijbs.8521 |
| Citation | Wu M, et al. (2014) Chondrocyte-specific knockout of Cbfbeta reveals the indispensable function of Cbfbeta in chondrocyte maturation, growth plate development and trabecular bone formation in mice. Int J Biol Sci 10(8):861-72 |
| abstractText | Despite years of research into bone formation, the mechanisms by which transcription factors specify growth plate development and trabecular bone formation remain unclear and the role of hypertrophic chondrocytes in trabeculae morphogenesis is controversial. To study the role of Core binding factor beta (Cbfbeta) in postnatal cartilage development and endochondral bone formation, we generated chondrocyte-specific Cbfbeta-deficient mice (Cbfbetaf/fCol2alpha1-Cre mice) using floxed alleles of Cbfbeta (Cbfbetaf/f) and Cre driven by the Collagen 2alpha1 promoter (Col2alpha1-Cre). Cbfbetaf/fCol2alpha1-Cre mice evaded developmental and newborn lethality to survive to adulthood and displayed severe skeletal malformation. Cbfbetaf/fCol2alpha1-Cre mice had dwarfism, hypoplastic skeletons, defective bone mineralization, shortened limbs, shortened sternum bodies, and un-calcified occipital bones and hyoid bones. In the long bone cartilage, the resting zone was elongated, and chondrocyte proliferation and hypertrophy were impaired in Cbfbetaf/fCol2alpha1-Cre mice, which led to deformation of the growth plates. Primary spongiosa formation was delayed, diaphysis was shortened and trabecular bone formation was almost absent in the mutant mice. In addition, lamellar bone formation in the secondary spongiosa was also impaired. However, osteoclast formation in the trabecular bone was not affected. Cbfbeta deficiency led to down-regulation of chondrocyte-regulating genes [i.e, patched (Ptc1), Cyclin D1 and Indian hedgehog (Ihh)] in the cartilage. Interestingly, the expression of Runx2 and Runx3 was not changed in the cartilage of the mutants. Collectively, the results revealed that Cbfbeta is crucial for postnatal skeletal development and endochondral bone formation through its function in growth plate development and chondrocyte proliferation and differentiation. This study also revealed that chondrocyte maturation, mediated by Cbfbeta, was critical to trabecular bone morphogenesis. Significantly, these findings provide insight into the role of Cbfbeta in postnatal skeletogenesis, which may assist in the development of new therapies for osteoporosis. |
