Senescence cell–associated extracellular vesicles serve as osteoarthritis disease and therapeutic markers
Aged, 80 and over
Cartilage, Articular
Male
0301 basic medicine
0303 health sciences
Primary Cell Culture
Middle Aged
Disease Models, Animal
Extracellular Vesicles
Mice
MicroRNAs
03 medical and health sciences
Chondrocytes
Osteoarthritis
Synovial Fluid
Animals
Humans
Drug Monitoring
Arthroplasty, Replacement, Knee
Biomarkers
Cells, Cultured
Cellular Senescence
Aged
DOI:
10.1172/jci.insight.125019
Publication Date:
2019-04-03T17:41:59Z
AUTHORS (13)
ABSTRACT
Senescent cells (SnCs) are increasingly recognized as central effector cells in age-related pathologies. Extracellular vesicles (EVs) are potential cellular communication tools through which SnCs exert central effector functions in the local tissue environment. To test this hypothesis in a medical indication that could be validated clinically, we evaluated EV production from SnCs enriched from chondrocytes isolated from human arthritic cartilage. EV production increased in a dose-responsive manner as the concentration of SnCs increased. The EVs were capable of transferring senescence to nonsenescent chondrocytes and inhibited cartilage formation by non-SnCs. microRNA (miR) profiles of EVs isolated from human arthritic synovial fluid did not fully overlap with the senescent chondrocyte EV profiles. The effect of SnC clearance was tested in a murine model of posttraumatic osteoarthritis. miR and protein profiles changed after senolytic treatment but varied depending on age. In young animals, senolytic treatment altered expression of miR-34a, -30c, -125a, -24, -92a, -150, and -186, and this expression correlated with cartilage production. The primary changes in EV contents in aged mice after senolytic treatment, which only reduced pain and degeneration, were immune related. In sum, EV contents found in synovial fluid may serve as a diagnostic for arthritic disease and indicator for therapeutic efficacy of senolytic treatment.
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