Cbfb enhances the osteogenic differentiation of both human and mouse mesenchymal stem cells induced by Cbfa-1 via reducing its ubiquitination-mediated degradation.
Core-binding factors are a small family of heterodimeric transcription factors that play critical roles in development. Whereas Cbfa-1, one of the three alpha subunits in the family, is essential for osteogenesis, Cbfb, the only beta 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.
Lien
Chun-Yang
CY
Institute of Biopharmaceutical Science, National Yang-Ming University, Shi-Pai, Taipei 11221, Taiwan, Republic of [corrected] China.
Lee
Oscar K
OK
Su
Yeu
Y
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D010012:Osteogenesis / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*
D050659:Core Binding Factor Alpha 1 Subunit; D050658:Core Binding Factor beta Subunit; D025801:Ubiquitin