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dc.contributor.authorScotece, Morena
dc.contributor.authorVaamonde-García, Carlos
dc.contributor.authorLechuga-Vieco, Ana Victoria
dc.contributor.authorCenteno Cortés, Alberto
dc.contributor.authorJiménez Gómez, María Concepción
dc.contributor.authorFilgueira-Fernández, Purificación
dc.contributor.authorRego-Pérez, Ignacio
dc.contributor.authorEnríquez, José Antonio
dc.contributor.authorBlanco García, Francisco J
dc.date.accessioned2022-09-06T10:40:21Z
dc.date.available2022-09-06T10:40:21Z
dc.date.issued2022-07-02
dc.identifier.citationScotece 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.issn1945-4589
dc.identifier.urihttp://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.sponsorshipThis 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.sponsorshipinfo: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 proteicoses_ES
dc.description.sponsorshipinfo: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 HPPes_ES
dc.description.sponsorshipInstituto de Salud Carlos III; RD16/0012/000
dc.description.sponsorshipXunta de Galicia; IN607A2021/07
dc.description.sponsorshipinfo: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.sponsorshipinfo: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.sponsorshipEspaña. Ministerio de Economía y Competitividad; RGP0016/2018
dc.language.isospaes_ES
dc.publisherImpact Journalses_ES
dc.relation.urihttps://doi.org/10.18632%2Faging.204153es_ES
dc.rightsCreative Commons Attribution 3.0 International License (CC-BY 3.0)es_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/*
dc.subjectAutophagyes_ES
dc.subjectConplastic micees_ES
dc.subjectmtDNAes_ES
dc.subjectOxidative stresses_ES
dc.subjectSenescencees_ES
dc.titlemtDNA variability determines spontaneous joint aging damage in a conplastic mouse modeles_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessinfo:eu-repo/semantics/openAccesses_ES
UDC.journalTitleAginges_ES
UDC.volume14es_ES
UDC.issue15es_ES
UDC.startPage5966es_ES
UDC.endPage5983es_ES


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