Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice

Ming Xu, Elizabeth W. Bradley, Megan M. Weivoda, Soyun M. Hwang, Tamar Pirtskhalava, Teresa Decklever, Geoffry L. Curran, Mikolaj Ogrodnik, Diana Jurk, Kurt O. Johnson, Val Lowe, Tamar Tchkonia, Jennifer J. Westendorf, James L. Kirkland

Research output: Contribution to journalArticlepeer-review

239 Scopus citations

Abstract

Osteoarthritis (OA) is the leading form of arthritis in the elderly, causing pain, disability, and immobility. OA has been associated with accumulation of senescent cells in or near joints. However, evidence for a causal link between OA and cellular senescence is lacking. Here, we present a novel senescent cell transplantation model involving injection of small numbers of senescent or nonsenescent cells from the ear cartilage of luciferase-expressing mice into the knee joint area of wild-type mice. By using bioluminescence and 18FDG PET imaging, we could track the injected cells in vivo for more than 10 days. Transplanting senescent cells into the knee region caused leg pain, impaired mobility, and radiographic and histological changes suggestive of OA. Transplanting nonsenescent cells had less of these effects. Thus, senescent cells can induce an OA-like state and targeting senescent cells could be a promising strategy for treating OA.

Original languageEnglish (US)
Pages (from-to)780-785
Number of pages6
JournalThe journals of gerontology. Series A, Biological sciences and medical sciences
Volume72
Issue number6
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.

Keywords

  • Bioluminescence imaging
  • Cell transplantation
  • Fluorodeoxyglucose
  • Mechanical allodynia
  • Senolytics

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