| First Author | Lim KE | Year | 2015 |
| Journal | J Bone Miner Res | Volume | 30 |
| Issue | 4 | Pages | 715-22 |
| PubMed ID | 25358268 | Mgi Jnum | J:222299 |
| Mgi Id | MGI:5644242 | Doi | 10.1002/jbmr.2397 |
| Citation | Lim KE, et al. (2015) Core binding factor beta of osteoblasts maintains cortical bone mass via stabilization of Runx2 in mice. J Bone Miner Res 30(4):715-22 |
| abstractText | Core binding factor beta (Cbfbeta), the partner protein of Runx family transcription factors, enhances Runx function by increasing the binding of Runx to DNA. Null mutations of Cbfb result in embryonic death, which can be rescued by restoring fetal hematopoiesis but only until birth, where bone formation is still nearly absent. Here, we address a direct role of Cbfbeta in skeletal homeostasis by generating osteoblast-specific Cbfbeta-deficient mice (Cbfb(Deltaob/Deltaob) ) from Cbfb-floxed mice crossed with mice expressing Cre from the Col1a1 promoter. Cbfb(Deltaob/Deltaob) mice showed normal growth and development but exhibited reduced bone mass, particularly of cortical bone. The reduction of bone mass in Cbfb(Deltaob/Deltaob) mice is similar to the phenotype of mice with haploinsufficiency of Runx2. Although the number of osteoblasts remained unchanged, the number of active osteoblasts decreased in Cbfb(Deltaob/Deltaob) mice and resulted in lower mineral apposition rate. Immunohistochemical and quantitative real-time PCR analyses showed that the expression of osteogenic markers, including Runx2, osterix, osteocalcin, and osteopontin, was significantly repressed in Cbfb(Deltaob/Deltaob) mice compared with wild-type mice. Cbfbeta deficiency also reduced Runx2 protein levels in osteoblasts. The mechanism was revealed by forced expression of Cbfbeta, which increased Runx2 protein levels in vitro by inhibiting polyubiquitination-mediated proteosomal degradation. Collectively, these findings indicate that Cbfbeta stabilizes Runx2 in osteoblasts by forming a complex and thus facilitates the proper maintenance of bone mass, particularly cortical bone. |
