| First Author | Wu M | Year | 2014 |
| Journal | Bone | Volume | 65 |
| Pages | 49-59 | PubMed ID | 24798493 |
| Mgi Jnum | J:214660 | Mgi Id | MGI:5603669 |
| Doi | 10.1016/j.bone.2014.04.031 | Citation | Wu M, et al. (2014) Deletion of core-binding factor beta (Cbfbeta) in mesenchymal progenitor cells provides new insights into Cbfbeta/Runxs complex function in cartilage and bone development. Bone 65:49-59 |
| abstractText | Core-binding factor beta (Cbfbeta) is a subunit of the Cbf family of heterodimeric transcription factors, which plays a critical role in skeletal development through its interaction with the Cbfalpha subunits, also known as Runt-related transcription factors (Runxs). However, the mechanism by which Cbfbeta regulates cartilage and bone development remains unclear. Existing Cbfbeta-deficient mouse models cannot specify the role of Cbfbeta in skeletal cell lineage. Herein, we sought to specifically address the role of Cbfbeta in cartilage and bone development by using a conditional knockout (CKO) approach. A mesenchymal-specific Cbfbeta CKO mouse model was generated by using the Dermo1-Cre mouse line to specifically delete Cbfbeta in mesenchymal stem cells, which give rise to osteoblasts and chondrocytes. Surprisingly, the mutant mice had under-developed larynx and tracheal cartilage, causing alveolus defects that led to death shortly after birth from suffocation. Also, the mutant mice exhibited severe skeletal deformities from defective intramembranous and endochondral ossification, owing to delayed chondrocyte maturation and impaired osteoblast differentiation. Almost all bones of the mutant mice, including the calvariae, vertebrae, tibiae, femurs, ribs, limbs and sternums were defective. Importantly, we showed that Cbfbeta was expressed throughout the skeleton during both embryonic and postnatal development, which explains the multiple-skeletal defects observed in the mutant mice. Consistently, Cbfbeta deficiency impaired both chondrocyte proliferation and hypertrophy zone hypertrophy during growth-plate development in the long bones of mutant mice. Notably, Cbfbeta, Runx1 and Runx2 displayed different expression patterns in the growth plates of the wild-type mice, indicating that Cbfbeta/Runx1 complex and Cbfbeta/Runx2 complex may regulate chondrocyte proliferation and hypertrophy, respectively, in a spatial and temporal manner. Cbfbeta deletion in the mesenchymal progenitors affected bone development by dramatically down-regulating Collagen X (Col X) and Osterix (Osx) but had a dispensable effect on osteoclast development. Collectively, the results demonstrate that Cbfbeta mediates cartilage and bone development by interacting with Runx1 and Runx2 to regulate the expressions of Col X and Osx for chondrocyte and osteoblast development. These findings not only reveal a critical role for Cbfbeta in cartilage and bone development but also facilitate the design of novel therapeutic approaches for skeletal diseases. |
