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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\/6<jats:sup>NZB<\/jats:sup> strain was developed with C57BL\/6JOlaHsd nuclear genome and NZB\/OlaHsdmtDNA while BL\/6<jats:sup>C57<\/jats:sup>, 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\/6<jats:sup>NZB<\/jats:sup> 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\/6<jats:sup>C57<\/jats:sup> mice. This was accompanied with higher autophagy and a lower apoptosis in the cartilage of BL\/6<jats:sup>NZB<\/jats:sup> 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\/6<jats:sup>NZB<\/jats:sup> ) mice develop less severe OA compared to the BL\/6<jats:sup>C57<\/jats:sup>original strain. These findings demonstrate that mitochondria and mtDNA are critical targets for potential novel therapeutic approaches to treat osteoarthritis.<\/jats:p>","DOI":"10.1038\/s41598-021-88083-0","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T10:13:30Z","timestamp":1619518410000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mitochondrial DNA impact on joint damaged process in a conplastic mouse model after being surgically induced with osteoarthritis"],"prefix":"10.1038","volume":"11","author":[{"given":"Morena","family":"Scotece","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Rego-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Victoria","family":"Lechuga-Vieco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto Centeno","family":"Cort\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Concepci\u00f3n","family":"Jim\u00e9nez-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purificaci\u00f3n","family":"Filgueira-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Vaamonde-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Enr\u00edquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,27]]},"reference":[{"key":"88083_CR1","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/nrrheum.2014.44","volume":"10","author":"DJ Hunter","year":"2014","unstructured":"Hunter, D. 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