2026-04-28T22:48:39Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/166962024-09-27T08:22:26Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Scotece, Morena
author
Vaamonde-García, Carlos
author
Lechuga-Vieco, Ana Victoria
author
Cortés, Alberto Centeno
author
Jimenez-Gomez, Maria Concepcion
author
Filgueira-Fernández, Purificación
author
Rego-Pérez, Ignacio
author
Enriquez, Jose Antonio
author
Blanco, Francisco J
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
2023-11-17T14:00:34Z
2023-11-17T14:00:34Z
2022-07-02
Aging (Albany NY). 2022 Jul 2;14(15):5966-5983.
http://hdl.handle.net/20.500.12105/16696
35779570
10.18632/aging.204153
1945-4589
Aging
Mitochondria and mtDNA variations contribute to specific aspects of the aging process. Here, we aimed to investigate the influence of mtDNA variation on joint damage in a model of aging using conplastic mice. A conplastic (BL/6NZB) mouse strain was developed with the C57BL/6JOlaHsd nuclear genome and NZB/OlaHsd mtDNA, for comparison with the original C57BL/6JOlaHsd strain (BL/6C57). Conplastic (BL/6NZB) and BL/6C57 mice were sacrificed at 25, 75, and 90 weeks of age. Hind knee joints were processed for histological analysis and joint pathology graded using the Mankin scoring system. By immunohistochemistry, cartilage expression of markers of autophagy (LC3, Beclin-1, and P62) and markers of senescence (MMP13, beta-Galactosidase, and p16) and proliferation (Ki67) were analyzed. We also measured the expression of 8-oxo-dG and cleaved caspase-3. Conplastic (BL/6NZB) mice presented lower Mankin scores at 25, 75, and 90 weeks of age, higher expression of LC3 and Beclin-1 and lower of P62 in cartilage than the original strain. Moreover, the downregulation of MMP13, beta-Galactosidase, and p16 was detected in cartilage from conplastic (BL/6NZB) mice, whereas higher Ki67 levels were detected in these mice. Finally, control BL/6C57 mice showed higher cartilage expression of 8-oxo-dG and cleaved caspase-3 than conplastic (BL/6NZB) mice. This study demonstrates that mtDNA genetic manipulation ameliorates joint aging damage in a conplastic mouse model, suggesting that mtDNA variability is a prognostic factor for aging-related osteoarthritis (OA) and that modulation of mitochondrial oxidative phosphorylation (OXPHOS) could be a novel therapeutic target for treating OA associated with aging.
eng
mtDNA variability determines spontaneous joint aging damage in a conplastic mouse model.
journal article
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https://repisalud.isciii.es/bitstreams/aadc369c-dd90-4c00-89f8-fbb4f0594d58/download
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mtDNA variability determines_Aging_2022.pdf
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https://repisalud.isciii.es/bitstreams/6281973f-d5c0-4dac-8d6f-94d6f53ddd5d/download
File
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8b28521c1e7f3bc4614fef8741b6e712
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text/plain
mtDNA variability determines_Aging_2022.pdf.txt