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.

Identification of a Novel Transcription Factor Required for Osteogenic Differentiation of Mesenchymal Stem Cells / Querques, F.; D'Agostino, Anna; Cozzolino, C.; Cozzuto, L.; Lombardo, B.; Leggiero, E.; Ruosi, C.; Pastore, L.. - In: STEM CELLS AND DEVELOPMENT. - ISSN 1547-3287. - 28:6(2019), pp. 370-383. [10.1089/scd.2018.0152]

Identification of a Novel Transcription Factor Required for Osteogenic Differentiation of Mesenchymal Stem Cells

Querques F.;D'AGOSTINO, ANNA;Cozzolino C.;Cozzuto L.;Lombardo B.;Leggiero E.;Ruosi C.;Pastore L.
2019

Abstract

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.
2019
Identification of a Novel Transcription Factor Required for Osteogenic Differentiation of Mesenchymal Stem Cells / Querques, F.; D'Agostino, Anna; Cozzolino, C.; Cozzuto, L.; Lombardo, B.; Leggiero, E.; Ruosi, C.; Pastore, L.. - In: STEM CELLS AND DEVELOPMENT. - ISSN 1547-3287. - 28:6(2019), pp. 370-383. [10.1089/scd.2018.0152]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/773466
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