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mtDNA variability determines spontaneous joint aging damage in a conplastic mouse model
dc.contributor.author | Scotece, Morena | |
dc.contributor.author | Vaamonde-García, Carlos | |
dc.contributor.author | Lechuga-Vieco, Ana Victoria | |
dc.contributor.author | Centeno Cortés, Alberto | |
dc.contributor.author | Jiménez Gómez, María Concepción | |
dc.contributor.author | Filgueira-Fernández, Purificación | |
dc.contributor.author | Rego-Pérez, Ignacio | |
dc.contributor.author | Enríquez, José Antonio | |
dc.contributor.author | Blanco García, Francisco J | |
dc.date.accessioned | 2022-09-06T10:40:21Z | |
dc.date.available | 2022-09-06T10:40:21Z | |
dc.date.issued | 2022-07-02 | |
dc.identifier.citation | Scotece M, Vaamonde-García C, Lechuga-Vieco AV, Cortés AC, Gómez MCJ, Filgueira-Fernández P, Rego-Pérez I, Enríquez JA, Blanco FJ. mtDNA variability determines spontaneous joint aging damage in a conplastic mouse model. Aging (Albany NY). 2022 Jul 2;14(15):5966-5983. | es_ES |
dc.identifier.issn | 1945-4589 | |
dc.identifier.uri | http://hdl.handle.net/2183/31510 | |
dc.description.abstract | [Abstract] 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. | es_ES |
dc.description.sponsorship | This work was supported by grants from Fondo de Investigación Sanitaria (PI16/02124, PI19/01206 and RETIC-RIER-RD16/0012/0002) integrated in the National Plan for Scientific Program, Development and Technological Innovation 2013–2016, and funded by the ISCIII-General Subdirection of Assessment and Promotion of Research-European Regional Development Fund (FEDER) “A way of making Europe”, by Grant IN607A2021/07 from GAIN, Xunta de Galicia (F.J.B.) and by CIBERFES-ISCIII, MINECO: SAF2015-65633-R, RTI2018-099357-B- I00, and HFSP (RGP0016/2018) to J.A.E. | es_ES |
dc.description.sponsorship | info:eu-repo/grantAgreement/MINECO/Programa Estatal de I+D+I Orientada a los Retos de la Sociedad/PI16%2F02124/ES/Determinación de índices predictivos de diagnóstico y pronóstico de artrosis de rodilla mediante la validación de biomarcadores proteicos | es_ES |
dc.description.sponsorship | info:eu-repo/grantAgreement/ISCIII/Programa Estatal de Generación de Conocimiento y Fortalecimiento del Sistema Español de I+D+I/PI19%2F01206/ES/VALIDACION CLINICA DE NUEVOS BIOMARCADORES PREDICTIVOS DE DIAGNOSTICO Y PRONOSTICO EN ARTROSIS: EL PROYECTO HPP | es_ES |
dc.description.sponsorship | Instituto de Salud Carlos III; RD16/0012/000 | |
dc.description.sponsorship | Xunta de Galicia; IN607A2021/07 | |
dc.description.sponsorship | info:eu-repo/grantAgreement/MINECO/Programa Estatal de I+D+I Orientada a los Retos de la Sociedad/SAF2015-65633-R/ES/FISIOPATOLOGIA DEL SISTEMA OXPHOS: GENETICA, AMBIENTE Y METABOLISMO | |
dc.description.sponsorship | info:eu-repo/grantAgreement/AEI/Programa Estatal de I+D+i Orientada a los Retos de la Sociedad/RTI2018-099357-B-I00/ES/EL SISTEMA OXPHOS DETERMINA EL METABOLISMO DEL ORGANISMO EN LA SALUD Y LA ENFERMEDAD | |
dc.description.sponsorship | España. Ministerio de Economía y Competitividad; RGP0016/2018 | |
dc.language.iso | spa | es_ES |
dc.publisher | Impact Journals | es_ES |
dc.relation.uri | https://doi.org/10.18632%2Faging.204153 | es_ES |
dc.rights | Creative Commons Attribution 3.0 International License (CC-BY 3.0) | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/ | * |
dc.subject | Autophagy | es_ES |
dc.subject | Conplastic mice | es_ES |
dc.subject | mtDNA | es_ES |
dc.subject | Oxidative stress | es_ES |
dc.subject | Senescence | es_ES |
dc.title | mtDNA variability determines spontaneous joint aging damage in a conplastic mouse model | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.access | info:eu-repo/semantics/openAccess | es_ES |
UDC.journalTitle | Aging | es_ES |
UDC.volume | 14 | es_ES |
UDC.issue | 15 | es_ES |
UDC.startPage | 5966 | es_ES |
UDC.endPage | 5983 | es_ES |
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