title: Paracrine effects of human adipose-derived mesenchymal stem cells in inflammatory stress-induced senescence features of osteoarthritic chondrocytes.
abstract: Aging and exposure to stress would determine the chondrocyte phenotype in osteoarthritis (OA). In particular, chronic inflammation may contribute to stress-induced senescence of chondrocytes and cartilage degeneration during OA progression. Recent studies have shown that adipose-derived mesenchymal stem cells exert paracrine effects protecting against degenerative changes in chondrocytes. We have investigated whether the conditioned medium (CM) from adipose-derived mesenchymal stem cells may regulate senescence features induced by inflammatory stress in OA chondrocytes. Our results indicate that CM down-regulated senescence markers induced by interleukin-1β including senescence-associated β-galactosidase activity, accumulation of γH2AX foci and morphological changes with enhanced formation of actin stress fibers. Treatment of chondrocytes with CM also decreased the production of oxidative stress, the activation of mitogen-activated protein kinases, and the expression of caveolin-1 and p21. The effects of CM were related to the reduction in p53 acetylation which would be dependent on the enhancement of Sirtuin 1 expression. Therefore, CM may exert protective effects in degenerative joint conditions by countering the premature senescence of OA chondrocytes induced by inflammatory stress.
authors.affiliation: Department of Pharmacology and IDM, University of Valencia, Burjasot, 46100 Valencia, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Platas
authors.affiliation: Department of Pharmacology and IDM, University of Valencia, Burjasot, 46100 Valencia, Spain.|Department of Pharmacy, Cardenal Herrera-CEU University, Moncada, 46113 Valencia, Spain.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Guillén
authors.affiliation: Department of Burn and Plastic Surgery, La Fe Polytechnic University Hospital, 46026 Valencia, Spain.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Pérez Del Caz
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gomar
authors.affiliation: Department of Orthopaedic Surgery and Traumatology, De la Ribera University Hospital, Alzira, 46600 Valencia, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Castejón
authors.affiliation: Valencia Transfusion Center, Generalitat Valenciana, 46014 Valencia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Mirabet
authors.affiliation: Department of Pharmacology and IDM, University of Valencia, Burjasot, 46100 Valencia, Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Alcaraz
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1 / Q000378:metabolism; D016922:Cellular Senescence / Q000502:physiology*; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D019899:Paracrine Communication / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D001616:beta-Galactosidase
keywords: adipose-derived mesenchymal stem cells conditioned medium; chondrocytes; inflammation; senescence