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TISSUE-SPECIFIC STEM CELLS

Cbfb Enhances the Osteogenic Differentiation of Both Human and Mouse Mesenchymal Stem Cells Induced by Cbfa-1 via Reducing Its Ubiquitination-Mediated Degradation

^aInstitute of Biopharmaceutical Science, National Yang-Ming University, Taipei, Taiwan, China;
^bDepartment of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, China;
^cInstitute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, China

Key Words. Mesenchymal stem cells • Cbfa-1 • Cbfb • Osteogenic differentiation • Ubiquitination

Correspondence: Yeu Su, Ph.D., Institute of Biopharmaceutical Science, National Yang-Ming University, Shi-Pai, Taipei 11221, Taiwan, China. Telephone: 886-2-28267143; Fax: 886-2-28250883; e-mail: yeusu{at}ym.edu.tw; or Oscar K. Lee, M.D., Ph.D., Institute of Clinical Medicine, National Yang-Ming University, Taipei Veterans General Hospital, 201, Sec 2, Shi-Pai Road, Taipei 11221, Taiwan, China. Telephone: 886-2-28757557; Fax: 886-2-28757657; e-mail: kslee{at}vghtpe.gov.tw

Received June 27, 2006; accepted for publication March 10, 2007.
First published online in STEM CELLS EXPRESS   March 22, 2007.



Core-binding factors are a small family of heterodimeric transcription factors that play critical roles in development. Whereas Cbfa-1, one of the three subunits in the family, is essential for osteogenesis, Cbfb, the only β subunit, forms heterodimers with different Cbfas to increase their DNA binding affinity by inducing conformational changes. Although defective bone formation was found in both Cbfa-1 and Cbfb knockout animals, the precise role of the latter in osteogenesis remains unclear. To dissect the contribution of Cbfb in osteogenic differentiation of mesenchymal stem cells (MSCs), recombinant adenoviruses carrying Cbfb (AdHACbfb) and Cbfa-1 (AdCbfa-1) were generated and used to infect both the mouse C3H10T1/2 cells and human bone marrow-derived MSCs. Although Cbfb alone failed to trigger osteogenesis of MSCs, it markedly enhanced the gene expression and enzyme activity of alkaline phosphatase as well as osteocalcin activation in those cells overexpressing Cbfa-1. Enhancement of the osteogenic differentiation-inducing effect of Cbfa-1 by Cbfb resulted from an increase in stability of the former due to the suppression of ubiquitination-mediated proteasomal degradation by the latter. Taken together, in addition to defining the role of Cbfb in osteogenic differentiation of MSCs, our results also suggest that the Cbfa-1 and Cbfb coexpressing MSCs might be an appropriate strategy for bone repairing and regeneration therapies.

Disclosure of potential conflicts of interest is found at the end of this article.