Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice
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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.
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- Authors
- Xu, M., Bradley, E. W., Weivoda, M. M., Hwang, S. M., Pirtskhalava, T., Decklever, T., Curran, G. L., Ogrodnik, M., Jurk, D., Johnson, K. O., Lowe, V., Tchkonia, T., Westendorf, J. J., & Kirkland, J. L.
- Affiliations
- Mayo Clinic (US)
- Newcastle University (GB)
- Corresponding author
- Kirkland, James L.
- ORCID
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-08-10
- Volume
- 72
- Issue
- 6
- Pages
- glw154
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC5861939
- OpenAlex
- W2515194864
- Cited by
- 352
- References
- 40
- Citations by year
- 2026: 9 · 2025: 34 · 2024: 51 · 2023: 44 · 2022: 37 · 2021: 52 · 2020: 46 · 2019: 37 · 2018: 23 · 2017: 17 · 2016: 1
- FWCI
- 27.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- The Journals of Gerontology Series A (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by-nc)
- Funders
- Howard Hughes Medical Institute
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- osteoarthritis, cellular senescence, knee joint, bioluminescence imaging, leg pain, mobility impairment, senolytics, animal models
- MeSH terms
- Animals, beta-Galactosidase, Fibroblasts, Injections, Intra-Articular, Luminescent Measurements, Mice, Inbred C57BL, Osteoarthritis, Stifle, Cellular Senescence, Radiopharmaceuticals, Fluorodeoxyglucose F18, Positron-Emission Tomography
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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