Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Downregulate Senescence Features in Osteoarthritic Osteoblasts.
Por:
Tofiño-Vian M, Guillén MI, Pérez Del Caz MD, Castejón MA and Alcaraz MJ
Publicada:
5 nov 2017
Resumen:
Osteoarthritis (OA) affects all articular tissues leading to pain and disability. The dysregulation of bone metabolism may contribute to the progression of this condition. Adipose-derived mesenchymal stem cells (ASC) are attractive candidates in the search of novel strategies for OA treatment and exert anti-inflammatory and cytoprotective effects on cartilage. Chronic inflammation in OA is a relevant factor in the development of cellular senescence and joint degradation. In this study, we extend our previous observations of ASC paracrine effects to study the influence of conditioned medium and extracellular vesicles from ASC on senescence induced by inflammatory stress in OA osteoblasts. Our results in cells stimulated with interleukin- (IL-) 1 indicate that conditioned medium, microvesicles, and exosomes from ASC downregulate senescence-associated -galactosidase activity and the accumulation of ? H2AX foci. In addition, they reduced the production of inflammatory mediators, with the highest effect on IL-6 and prostaglandin E 2 . The control of mitochondrial membrane alterations and oxidative stress may provide a mechanism for the protective effects of ASC in OA osteoblasts. We have also shown that microvesicles and exosomes mediate the paracrine effects of ASC. Our study suggests that correction of abnormal osteoblast metabolism by ASC products may contribute to their protective effects.
Filiaciones:
Tofiño-Vian M:
Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Av. Vicent A. Estellés s/n, Burjasot, 46100 Valencia, Spain
Guillén MI:
Department of Pharmacy, Cardenal Herrera-CEU University, Ed. Ciencias de la Salud, Alfara, 46115 Valencia, Spain
Pérez Del Caz MD:
Department of Burn and Plastic Surgery, La Fe Polytechnic University Hospital, 46026 Valencia, Spain
:
Department of Orthopaedic Surgery and Traumatology, De la Ribera University Hospital, Alzira, 46600 Valencia, Spain
Alcaraz MJ:
Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Av. Vicent A. Estellés s/n, Burjasot, 46100 Valencia, Spain
|