title: Lamin A deregulation in human mesenchymal stem cells promotes an impairment in their chondrogenic potential and imbalance in their response to oxidative stress.
abstract: 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.
authors.affiliation: Rheumatology Division, ProteoRed/ISCIII, INIBIC-Hospital Universitario A Coruña, 15006 A Coruña, Spain; CIBER-BBN, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Mateos
authors.forename: Alexandre
authors.initials: A
authors.lastname: De la Fuente
authors.forename: Iván
authors.initials: I
authors.lastname: Lesende-Rodriguez
authors.forename: Pablo
authors.initials: P
authors.lastname: Fernández-Pernas
authors.forename: María C
authors.initials: MC
authors.lastname: Arufe
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
mesh_terms: D050156:Adipogenesis; D002454:Cell Differentiation; D002478:Cells, Cultured; D020219:Chondrogenesis; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D034904:Lamin Type A; D009687:Nuclear Proteins; D011498:Protein Precursors; D017382:Reactive Oxygen Species; C090764:prelamin A; D013482:Superoxide Dismutase
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