Senescence cell–associated extracellular vesicles serve as osteoarthritis disease and therapeutic markers

Ok Hee Jeon, David R. Wilson, Cristina C. Clement, Sona Rathod, Christopher Cherry, Bonita Powell, Zhenghong Lee, Ahmad M. Khalil, Jordan Green, Judith Campisi, Laura Santambrogio, Kenneth Whitaker Witwer, Jennifer Hartt Elisseeff

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere125019
JournalJCI Insight
Volume4
Issue number7
DOIs
StatePublished - Apr 4 2019

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Osteoarthritis
Chondrocytes
MicroRNAs
Arthritis
Cartilage
Synovial Fluid
Therapeutics
Extracellular Vesicles
Communication
Pathology
Pain
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Senescence cell–associated extracellular vesicles serve as osteoarthritis disease and therapeutic markers. / Jeon, Ok Hee; Wilson, David R.; Clement, Cristina C.; Rathod, Sona; Cherry, Christopher; Powell, Bonita; Lee, Zhenghong; Khalil, Ahmad M.; Green, Jordan; Campisi, Judith; Santambrogio, Laura; Witwer, Kenneth Whitaker; Elisseeff, Jennifer Hartt.

In: JCI Insight, Vol. 4, No. 7, e125019, 04.04.2019.

Research output: Contribution to journalArticle

Jeon, OH, Wilson, DR, Clement, CC, Rathod, S, Cherry, C, Powell, B, Lee, Z, Khalil, AM, Green, J, Campisi, J, Santambrogio, L, Witwer, KW & Elisseeff, JH 2019, 'Senescence cell–associated extracellular vesicles serve as osteoarthritis disease and therapeutic markers', JCI Insight, vol. 4, no. 7, e125019. https://doi.org/10.1172/jci.insight.125019
Jeon, Ok Hee ; Wilson, David R. ; Clement, Cristina C. ; Rathod, Sona ; Cherry, Christopher ; Powell, Bonita ; Lee, Zhenghong ; Khalil, Ahmad M. ; Green, Jordan ; Campisi, Judith ; Santambrogio, Laura ; Witwer, Kenneth Whitaker ; Elisseeff, Jennifer Hartt. / Senescence cell–associated extracellular vesicles serve as osteoarthritis disease and therapeutic markers. In: JCI Insight. 2019 ; Vol. 4, No. 7.
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