Lamin A deregulation in human mesenchymal stem cells promotes an impairment in their chondrogenic potential and imbalance in their response to oxidative stress

In the present study, we examined the effect of the over-expression of LMNA, or its mutant form progerin (PG), on the mesoderm differentiation potential of mesenchymal stem cells (MSCs) from human umbilical cord (UC) stroma using a recently described differentiation model employing spheroid formatio...

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Bibliographic Details
Published in:Stem cell research 2013-11, Vol.11 (3), p.1137-1148
Main Authors: Mateos, Jesús, De la Fuente, Alexandre, Lesende-Rodriguez, Iván, Fernández-Pernas, Pablo, Arufe, María C., Blanco, Francisco J.
Format: Article
Language:English
Subjects:
Adipogenesis
Cell Differentiation
Cells, Cultured
Chondrogenesis
Humans
Lamin Type A - genetics
Lamin Type A - metabolism
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - enzymology
Mesenchymal Stromal Cells - metabolism
Mitochondria - metabolism
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Oxidative Stress
Protein Precursors - genetics
Protein Precursors - metabolism
Reactive Oxygen Species - metabolism
Superoxide Dismutase - metabolism
Umbilical Cord - cytology
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Summary:In the present study, we examined the effect of the over-expression of LMNA, or its mutant form progerin (PG), on the mesoderm differentiation potential of mesenchymal stem cells (MSCs) from human umbilical cord (UC) stroma using a recently described differentiation model employing spheroid formation. Accumulation of lamin A (LMNA) was previously associated with the osteoarthritis (OA) chondrocyte phenotype. Mutations of this protein are linked to laminopathies and specifically to Hutchinson–Gilford Progeria Syndrome (HGPS), an accelerated aging disease. Some authors have proposed that a deregulation of LMNA affects the differentiation potential of stem cells. The chondrogenic potential is defective in PG-MSCs, although both PG and LMNA transduced MSCs, have an increase in hypertrophy markers during chondrogenic differentiation. Furthermore, both PG and LMNA-MSCs showed a decrease in manganese superoxide dismutase (MnSODM), an increase of mitochondrial MnSODM-dependent reactive oxygen species (ROS) and alterations in their migration capacity. Finally, defects in chondrogenesis are partially reversed by periodic incubation with ROS-scavenger agent that mimics MnSODM effect. Our results indicate that over-expression of LMNA or PG by lentiviral gene delivery leads to defects in chondrogenic differentiation potential partially due to an imbalance in oxidative stress. •Over-expression of LMNA and PG reduces chondrogenic capacity of MSC.•MSCs transduced with PG or LMNA express low level of MnSODM.•MSCs transduced with PG and LMNA produce high level of ROS.•ROS reduces the chondrogenic capacity of MSC.•NAC improves the chondrogenic capacity of MSCs transduced with LMNA/PG.
ISSN:1873-5061
1876-7753
DOI:10.1016/j.scr.2013.07.004