Paracrine effects of human adipose-derived mesenchymal stem cells in inflammatory stress-induced senescence features of osteoarthritic chondrocytes

Autors de IIS La Fe

• María Dolores Pérez Del Caz

  Autor

Autors aliens a IIS La Fe

• Platas J
• Guillen MI
• Gomar F
• Castejon MA
• Mirabet V
• Alcaraz MJ

Grups d'Investigació

• Dermatología y Regeneración Tisular

  

  Leader

  Rafael Botella Estrada

• Regeneración y Trasplante Cardíaco

  

  Leader

  Pilar Sepúlveda Sanchis

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-1 beta including senescence-associated beta-galactosidase activity, accumulation of gamma H2AX 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.

Keywords

• adipose-derived mesenchymal stem cells conditioned medium; inflammation; senescence; chondrocytes