Forced expression of mouse progerin attenuates the osteoblast differentiation interrupting ß-catenin signal pathway in vitro.
Cell Tissue Res
; 375(3): 655-664, 2019 Mar.
Article
en En
| MEDLINE
| ID: mdl-30284086
ABSTRACT
Nuclear protein, lamin A, which is a component of inner membrane on nucleoplasm, plays a role in nuclear formation and cell differentiation. The expression of mutated lamin A, termed progerin, causes a rare genetic aging disorder, Hutchinson-Gilford progeria syndrome, which shows abnormal bone formation with the decrease in a number of osteoblasts and osteocytes. However, exact molecular mechanism how progerin exerts depressive effects on osteogenesis has not been fully understood. Here, we created mouse lamin A dC50 cDNA encoding progerin that lacks 50 amino acid residues at C-terminus, transfected it in mouse preosteoblast-like MC3T3-E1 cells, and examined the changes in osteoblast phenotype. When lamin A dC50-expressed cells were cultured with differentiation-inductive medium, alkaline phosphatase (ALP) activity and mRNA levels of major osteoblast markers, type I collagen (Col1), bone sialoprotein (BSP), dentine matrix protein 1 (DMP1), and Runx2 were significantly decreased, and no mineralized nodules were detected as seen in control cells expressing empty vector. In the culture with mineralization-inductive medium, mRNA levels of BSP, osteocalcin, DMP1, Runx2, and osterix were strongly decreased parallel with loss of mineralization in lamin A dC50-expressed cells, while mineralized nodules appear at 21 days in control cells. Furthermore, lamin A dC50 expression was depressed nuclear localization of ß-catenin with the decrease of GSK-3ß phosphorylation level. These results suggest that lamin A dC50 depresses osteoblast differentiation in both early and late stages, and it negatively regulates ß-catenin activity interacting with GSK-3ß in cytoplasm.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Osteoblastos
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Transducción de Señal
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Diferenciación Celular
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Lamina Tipo A
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Beta Catenina
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cell Tissue Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón