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.
Keywords: ADIPOQ; AGG; ALP; DMEM; Dulbecco's Modified Eagles Medium; ECM; FABP; GFP; HGPS; Hutchinson–Gilford Progeria Syndrome; IL-8; LMNA; LPL; MSCs; MnSODM; OA; OC; PG; ROS; RPLP; RT-PCR; Ribosomal Protein Large P1; SDF-1; UC; adiponectin; aggrecan; alkaline phosphatase; extracellular matrix; fatty acid binding protein; green fluorescent protein; interleukin 8; lamin A; lipoprotein lipase; manganese superoxide dismutase; mesenchymal stem cells; osteoarthritis; osteocalcin; progerin; reactive oxygen species; real-time polymerase chain reaction; stromal cell-derived factor 1; umbilical cord.
© 2013.