Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice

Ming Xu, Elizabeth Bradley, Megan 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 journalArticle

56 Citations (Scopus)

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

Fingerprint

Osteoarthritis
Ear Cartilage
Pain
Cell Aging
Cell Transplantation
Fluorodeoxyglucose F18
Knee Joint
Luciferases
Arthritis
Leg
Knee
Joints
Injections

Keywords

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

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice. / Xu, Ming; Bradley, Elizabeth; Weivoda, Megan; Hwang, Soyun M.; Pirtskhalava, Tamar; Decklever, Teresa; Curran, Geoffry L.; Ogrodnik, Mikolaj; Jurk, Diana; Johnson, Kurt O.; Lowe, Val; Tchkonia, Tamar; Westendorf, Jennifer J; Kirkland, James L.

In: The journals of gerontology. Series A, Biological sciences and medical sciences, Vol. 72, No. 6, 01.06.2017, p. 780-785.

Research output: Contribution to journalArticle

Xu, Ming ; Bradley, Elizabeth ; Weivoda, Megan ; Hwang, Soyun M. ; Pirtskhalava, Tamar ; Decklever, Teresa ; Curran, Geoffry L. ; Ogrodnik, Mikolaj ; Jurk, Diana ; Johnson, Kurt O. ; Lowe, Val ; Tchkonia, Tamar ; Westendorf, Jennifer J ; Kirkland, James L. / Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice. In: The journals of gerontology. Series A, Biological sciences and medical sciences. 2017 ; Vol. 72, No. 6. pp. 780-785.
@article{58119724c8bd441c9df70288d47558e6,
title = "Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice",
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.",
keywords = "Bioluminescence imaging, Cell transplantation, Fluorodeoxyglucose, Mechanical allodynia, Senolytics",
author = "Ming Xu and Elizabeth Bradley and Megan Weivoda and Hwang, {Soyun M.} and Tamar Pirtskhalava and Teresa Decklever and Curran, {Geoffry L.} and Mikolaj Ogrodnik and Diana Jurk and Johnson, {Kurt O.} and Val Lowe and Tamar Tchkonia and Westendorf, {Jennifer J} and Kirkland, {James L}",
year = "2017",
month = "6",
day = "1",
doi = "10.1093/gerona/glw154",
language = "English (US)",
volume = "72",
pages = "780--785",
journal = "Journals of Gerontology - Series A Biological Sciences and Medical Sciences",
issn = "1079-5006",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice

AU - Xu, Ming

AU - Bradley, Elizabeth

AU - Weivoda, Megan

AU - Hwang, Soyun M.

AU - Pirtskhalava, Tamar

AU - Decklever, Teresa

AU - Curran, Geoffry L.

AU - Ogrodnik, Mikolaj

AU - Jurk, Diana

AU - Johnson, Kurt O.

AU - Lowe, Val

AU - Tchkonia, Tamar

AU - Westendorf, Jennifer J

AU - Kirkland, James L

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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.

KW - Bioluminescence imaging

KW - Cell transplantation

KW - Fluorodeoxyglucose

KW - Mechanical allodynia

KW - Senolytics

UR - http://www.scopus.com/inward/record.url?scp=85027520811&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027520811&partnerID=8YFLogxK

U2 - 10.1093/gerona/glw154

DO - 10.1093/gerona/glw154

M3 - Article

VL - 72

SP - 780

EP - 785

JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

SN - 1079-5006

IS - 6

ER -