The Role of the Nuclear Envelope Protein MAN1 in Mesenchymal Stem Cell Differentiation
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Fecha
2017-04
Autores
Bermeo, Sandra
Al-Saedi, Ahmed
Kassem, Moustapha
Vidal, Christopher
Duque, Gustavo
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Editor
DeepDyve
Resumen
Mutations in MAN1, a protein of the nuclear envelope, cause bone phenotypes characterized by hyperostosis. The mechanism of this proosteogenic
phenotype remains unknown. We increased and decreased MAN1 expression in mesenchymal stem cells (MSC) upon which
standard osteogenic and adipogenic differentiation were performed. MAN1 knockdown increased osteogenesis and mineralization. In
contrast, osteogenesis remained stable upon MAN1 overexpression. Regarding a mechanism, we found that low levels of MAN1 facilitated the
nuclear accumulation of regulatory smads and smads-related complexes, with a concurrently high expression of nuclear b-Catenin. In
addition, we found adipogenesis to be decreased in both conditions, although predominantly affected by MAN1 overexpression. Finally, lamin
A, a protein of the nuclear envelope that regulates MSC differentiation, was unaffected by changes in MAN1. In conclusion, our studies
demonstrated that lower levels of MAN1 in differentiating MSC are associated with higher osteogenesis and lower adipogenesis. High levels of
MAN1 only affected adipogenesis. These effects could have an important role in the understanding of the role of the proteins of the nuclear
envelope in bone formation. J. Cell. Biochem. 118: 4425–4435, 2017.
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Palabras clave
Mesenchymal stem cells, Osteoblastogenesis, Adipogenesis, Man1, Lamin A