Regulación de la Osteogénesis en Células Madre/Estromales Mesenquimales Humanas por el parálogo 14-3-3?
14-3-3 proteins are key modulators of phosphorylated proteins, acting as integrative hubs in multiple signaling networks. Although the 14-3-3 protein family (?, ?, ?, ?, ?, ?, and ?) has been implicated in various processes relevant to osteogenesis, the specific role of each paralog remains unknown....
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
2024
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_7883 https://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_7883.dir/7883.PDF |
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| Sumario: | 14-3-3 proteins are key modulators of phosphorylated proteins, acting as integrative hubs in multiple signaling networks. Although the 14-3-3 protein family (?, ?, ?, ?, ?, ?, and ?) has been implicated in various processes relevant to osteogenesis, the specific role of each paralog remains unknown. This PhD Thesis has deepened the knowledge of the function of the 14-3-3? protein in regulating the osteogenic differentiation of human adipose-derived mesenchymal stem/stromal cells (hASC). Through the integration of biochemical, molecular, and bioinformatic studies, it has been demonstrated that 14-3-3? exerts a dual effect on the regulation of the osteogenic commitment. The increase in 14-3-3? levels at an early stage of osteogenesis helps to appropriately control high metabolic activity and energy production, modulating endoplasmic reticulum stress and regulating the antioxidant response, thereby ensuring proper protein synthesis and extracellular matrix maturation. Conversely, the reduction of its levels at an advanced stage plays a crucial role in the induction of mineralization. These findings suggest the potential to develop targeted therapies for bone pathologies through the specific modulation of 14-3-3?. |
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