Mitochondrial DNA impact on joint damaged process in a conplastic mouse model after being surgically induced with osteoarthritis

Abstract It has been suggested that mitochondrial dysfunction and mtDNA variations may contribute to osteoarthritis (OA) pathogenesis. However, the causative link to support this claim is lacking. Here, we surgically-induced OA in conplastic mice in order to evaluate the functional consequences of m...

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Autores principales:	Morena Scotece, Ignacio Rego-Pérez, Ana Victoria Lechuga-Vieco, Alberto Centeno Cortés, María Concepción Jiménez-Gómez, Purificación Filgueira-Fernández, Carlos Vaamonde-García, José Antonio Enríquez, Francisco J. Blanco
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b5574bd366dc4090abea5086ff794bf4
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spelling	oai:doaj.org-article:b5574bd366dc4090abea5086ff794bf42021-12-02T13:41:34ZMitochondrial DNA impact on joint damaged process in a conplastic mouse model after being surgically induced with osteoarthritis10.1038/s41598-021-88083-02045-2322https://doaj.org/article/b5574bd366dc4090abea5086ff794bf42021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88083-0https://doaj.org/toc/2045-2322Abstract It has been suggested that mitochondrial dysfunction and mtDNA variations may contribute to osteoarthritis (OA) pathogenesis. However, the causative link to support this claim is lacking. Here, we surgically-induced OA in conplastic mice in order to evaluate the functional consequences of mtDNA haplotypes in their joint degeneration. BL/6NZB strain was developed with C57BL/6JOlaHsd nuclear genome and NZB/OlaHsdmtDNA while BL/6C57, which is the original, was developed with C57BL/6JOlaHsd nuclear genome and C57/OlaHsdmtDNA for comparison. The surgical DMM OA model was induced in both strains. Their knees were processed and examined for histopathological changes. Cartilage expression of markers of autophagy, apoptosis, oxidative stress and senescence were also analyzed by immunohistochemistry. The joints of BL/6NZB mice that were operated presented more cellularity together with a reduced OARSI histopathology score, subchondral bone, menisci score and synovitis compared to those of BL/6C57 mice. This was accompanied with higher autophagy and a lower apoptosis in the cartilage of BL/6NZB mice that were operated. Therefore, the study demonstrates the functional impact of non-pathological variants of mtDNA on OA process using a surgically-induced OA model. Conplastic (BL/6NZB ) mice develop less severe OA compared to the BL/6C57original strain. These findings demonstrate that mitochondria and mtDNA are critical targets for potential novel therapeutic approaches to treat osteoarthritis.Morena ScoteceIgnacio Rego-PérezAna Victoria Lechuga-ViecoAlberto Centeno CortésMaría Concepción Jiménez-GómezPurificación Filgueira-FernándezCarlos Vaamonde-GarcíaJosé Antonio EnríquezFrancisco J. BlancoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Morena Scotece Ignacio Rego-Pérez Ana Victoria Lechuga-Vieco Alberto Centeno Cortés María Concepción Jiménez-Gómez Purificación Filgueira-Fernández Carlos Vaamonde-García José Antonio Enríquez Francisco J. Blanco Mitochondrial DNA impact on joint damaged process in a conplastic mouse model after being surgically induced with osteoarthritis
description	Abstract It has been suggested that mitochondrial dysfunction and mtDNA variations may contribute to osteoarthritis (OA) pathogenesis. However, the causative link to support this claim is lacking. Here, we surgically-induced OA in conplastic mice in order to evaluate the functional consequences of mtDNA haplotypes in their joint degeneration. BL/6NZB strain was developed with C57BL/6JOlaHsd nuclear genome and NZB/OlaHsdmtDNA while BL/6C57, which is the original, was developed with C57BL/6JOlaHsd nuclear genome and C57/OlaHsdmtDNA for comparison. The surgical DMM OA model was induced in both strains. Their knees were processed and examined for histopathological changes. Cartilage expression of markers of autophagy, apoptosis, oxidative stress and senescence were also analyzed by immunohistochemistry. The joints of BL/6NZB mice that were operated presented more cellularity together with a reduced OARSI histopathology score, subchondral bone, menisci score and synovitis compared to those of BL/6C57 mice. This was accompanied with higher autophagy and a lower apoptosis in the cartilage of BL/6NZB mice that were operated. Therefore, the study demonstrates the functional impact of non-pathological variants of mtDNA on OA process using a surgically-induced OA model. Conplastic (BL/6NZB ) mice develop less severe OA compared to the BL/6C57original strain. These findings demonstrate that mitochondria and mtDNA are critical targets for potential novel therapeutic approaches to treat osteoarthritis.
format	article
author	Morena Scotece Ignacio Rego-Pérez Ana Victoria Lechuga-Vieco Alberto Centeno Cortés María Concepción Jiménez-Gómez Purificación Filgueira-Fernández Carlos Vaamonde-García José Antonio Enríquez Francisco J. Blanco
author_facet	Morena Scotece Ignacio Rego-Pérez Ana Victoria Lechuga-Vieco Alberto Centeno Cortés María Concepción Jiménez-Gómez Purificación Filgueira-Fernández Carlos Vaamonde-García José Antonio Enríquez Francisco J. Blanco
author_sort	Morena Scotece
title	Mitochondrial DNA impact on joint damaged process in a conplastic mouse model after being surgically induced with osteoarthritis
title_short	Mitochondrial DNA impact on joint damaged process in a conplastic mouse model after being surgically induced with osteoarthritis
title_full	Mitochondrial DNA impact on joint damaged process in a conplastic mouse model after being surgically induced with osteoarthritis
title_fullStr	Mitochondrial DNA impact on joint damaged process in a conplastic mouse model after being surgically induced with osteoarthritis
title_full_unstemmed	Mitochondrial DNA impact on joint damaged process in a conplastic mouse model after being surgically induced with osteoarthritis
title_sort	mitochondrial dna impact on joint damaged process in a conplastic mouse model after being surgically induced with osteoarthritis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b5574bd366dc4090abea5086ff794bf4
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Mitochondrial DNA impact on joint damaged process in a conplastic mouse model after being surgically induced with osteoarthritis

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