| First Author | Querques F | Year | 2019 |
| Journal | Stem Cells Dev | Volume | 28 |
| Issue | 6 | Pages | 370-383 |
| PubMed ID | 30654721 | Mgi Jnum | J:314087 |
| Mgi Id | MGI:6810800 | Doi | 10.1089/scd.2018.0152 |
| Citation | Querques F, et al. (2019) Identification of a Novel Transcription Factor Required for Osteogenic Differentiation of Mesenchymal Stem Cells. Stem Cells Dev 28(6):370-383 |
| abstractText | Osteogenic differentiation is a complex and still poorly understood biological process regulated by intrinsic cellular signals and extrinsic microenvironmental cues. Following appropriate stimuli, mesenchymal stem cells (MSCs) differentiate into osteoblasts through a tightly regulated multistep process driven by several transcription factors and characterized by the expression of a number of bone-specific proteins. In this study, we describe a novel transcription factor that we named osteoblast inducer (ObI)-1, involved in MSC differentiation toward the osteogenic lineage. ObI-1 encodes for a nuclear protein subjected to proteasomal degradation and expressed during osteoblast differentiation both in a murine multipotent mesenchymal cell line (W20-17) and in primary murine MSCs. RNA interference-mediated knockdown of ObI-1 expression significantly impairs osteoblast differentiation and matrix mineralization with reduced expression of the osteogenic markers, Runt-related transcription factor 2 (Runx2) and osteopontin. Conversely, ObI-1 overexpression enhances osteogenic differentiation and bone-specific markers expression. ObI-1 stimulates bone morphogenetic protein (BMP)-4 expression and the consequent activation of the Smad pathway; treatment with a BMP receptor type I antagonist completely abolishes ObI-1-mediated stimulation of osteogenic differentiation. Collectively, our findings suggest that ObI-1 modulates osteogenic differentiation, at least in part, through the BMP signaling pathway, increasing Runx2 activation and leading to osteoblast commitment and maturation. |
