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.
authors: Robert and Arlene Kogod Center on Aging.
authors: Ming
authors: M
authors: Xu
authors: Department of Orthopedic Surgery.
authors: Elizabeth W
authors: EW
authors: Bradley
authors: Robert and Arlene Kogod Center on Aging.
authors: Megan M
authors: MM
authors: Weivoda
authors: Mayo Medical School, and.
authors: Soyun M
authors: SM
authors: Hwang
authors: Robert and Arlene Kogod Center on Aging.
authors: Tamar
authors: T
authors: Pirtskhalava
authors: Department of Radiology, Mayo Clinic, Rochester, Minnesota.
authors: Teresa
authors: T
authors: Decklever
authors: Department of Radiology, Mayo Clinic, Rochester, Minnesota.
authors: Geoffry L
authors: GL
authors: Curran
authors: Robert and Arlene Kogod Center on Aging.|Newcastle University Institute for Ageing and Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
authors: Mikolaj
authors: M
authors: Ogrodnik
authors: Newcastle University Institute for Ageing and Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
authors: Diana
authors: D
authors: Jurk
authors: Robert and Arlene Kogod Center on Aging.
authors: Kurt O
authors: KO
authors: Johnson
authors: Department of Radiology, Mayo Clinic, Rochester, Minnesota.
authors: Val
authors: V
authors: Lowe
authors: Robert and Arlene Kogod Center on Aging.
authors: Tamar
authors: T
authors: Tchkonia
authors: Department of Orthopedic Surgery.|Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN.
authors: Jennifer J
authors: JJ
authors: Westendorf
authors: Robert and Arlene Kogod Center on Aging.
authors: James L
authors: JL
authors: Kirkland
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D005347:Fibroblasts / Q000528:radiation effects / Q000637:transplantation*; D019788:Fluorodeoxyglucose F18; D007270:Injections, Intra-Articular; D008163:Luminescent Measurements; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000209:etiology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013264:Stifle / Q000000981:diagnostic imaging; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C061901:GLB1 protein, human; D001616:beta-Galactosidase
keywords: Bioluminescence imaging; Cell transplantation; Fluorodeoxyglucose; Mechanical allodynia; Senolytics