{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:26:24Z","timestamp":1790720784904,"version":"4.1.0"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T00:00:00Z","timestamp":1580169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T00:00:00Z","timestamp":1580169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mitochondrial mutations and dysfunction have been demonstrated in several age-related disorders including osteoarthritis, yet its relative contribution to pathogenesis remains unknown. Here we evaluated whether premature aging caused by accumulation of mitochondrial DNA mutations in <jats:italic>Polg<\/jats:italic><jats:sup><jats:italic>D<\/jats:italic>2<jats:italic>75A<\/jats:italic><\/jats:sup> mice predisposes to the development of knee osteoarthritis. Compared with wild type animals, homozygous <jats:italic>Polg<\/jats:italic><jats:sup><jats:italic>D275A<\/jats:italic><\/jats:sup> mice displayed a specific bone phenotype characterized by osteopenia of epiphyseal trabecular bone and subchondral cortical plate. Trabecular thickness was significantly associated with osteocyte apoptosis rates and osteoclasts numbers were increased in subchondral bone tissues. While chondrocyte apoptosis rates in articular and growth plate cartilage were similar between groups, homozygous mitochondrial DNA mutator mice displayed elevated numbers of hypertrophic chondrocytes in articular calcified cartilage. Low grade cartilage degeneration, predominantly loss of proteoglycans, was present in all genotypes and the development of osteoarthritis features was not found accelerated in premature aging. Somatically acquired mitochondrial DNA mutations predispose to elevated subchondral bone turnover and hypertrophy in calcified cartilage, yet additional mechanical or metabolic stimuli would seem required for induction and accelerated progression of aging-associated osteoarthritis.<\/jats:p>","DOI":"10.1038\/s41598-020-58385-w","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T11:03:18Z","timestamp":1580209398000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Prematurely aging mitochondrial DNA mutator mice display subchondral osteopenia and chondrocyte hypertrophy without further osteoarthritis features"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4367-4641","authenticated-orcid":false,"given":"Jeroen","family":"Geurts","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Nasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Distel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"M\u00fcller-Gerbl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas A.","family":"Prolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory C.","family":"Kujoth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich A.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"H\u00fcgle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,28]]},"reference":[{"key":"58385_CR1","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1136\/annrheumdis-2016-210131","volume":"76","author":"M Fernandez-Moreno","year":"2017","unstructured":"Fernandez-Moreno, M. et al. Mitochondrial DNA haplogroups influence the risk of incident knee osteoarthritis in OAI and CHECK cohorts. A meta-analysis and functional study. Annals of the rheumatic diseases 76, 1114\u20131122, https:\/\/doi.org\/10.1136\/annrheumdis-2016-210131 (2017).","journal-title":"Annals of the rheumatic diseases"},{"key":"58385_CR2","doi-asserted-by":"publisher","unstructured":"Delco, M. L., Bonnevie, E. D., Bonassar, L. J. & Fortier, L. A. Mitochondrial dysfunction is an acute response of articular chondrocytes to mechanical injury. Journal of orthopaedic research: official publication of the Orthopaedic Research Society, https:\/\/doi.org\/10.1002\/jor.23651 (2017).","DOI":"10.1002\/jor.23651"},{"issue":"8","key":"58385_CR3","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1016\/j.joca.2017.07.020","volume":"26","author":"M.Y. Ansari","year":"2018","unstructured":"Ansari, M. Y., Khan, N. M., Ahmad, I. & Haqqi, T. M. Parkin clearance of dysfunctional mitochondria regulates ROS levels and increases survival of human chondrocytes. Osteoarthritis and cartilage, https:\/\/doi.org\/10.1016\/j.joca.2017.07.020 (2017).","journal-title":"Osteoarthritis and Cartilage"},{"key":"58385_CR4","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/nrrheum.2010.213","volume":"7","author":"FJ Blanco","year":"2011","unstructured":"Blanco, F. J., Rego, I. & Ruiz-Romero, C. The role of mitochondria in osteoarthritis. Nature reviews. Rheumatology 7, 161\u2013169, https:\/\/doi.org\/10.1038\/nrrheum.2010.213 (2011).","journal-title":"Nature reviews. Rheumatology"},{"key":"58385_CR5","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1016\/j.joca.2018.06.016","volume":"26","author":"I Rego-Perez","year":"2018","unstructured":"Rego-Perez, I. et al. Mitochondrial DNA haplogroups associated with MRI-detected structural damage in early knee osteoarthritis. Osteoarthritis and cartilage 26, 1562\u20131569, https:\/\/doi.org\/10.1016\/j.joca.2018.06.016 (2018).","journal-title":"Osteoarthritis and cartilage"},{"key":"58385_CR6","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nature02517","volume":"429","author":"A Trifunovic","year":"2004","unstructured":"Trifunovic, A. et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429, 417\u2013423, https:\/\/doi.org\/10.1038\/nature02517 (2004).","journal-title":"Nature"},{"key":"58385_CR7","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1126\/science.1112125","volume":"309","author":"GC Kujoth","year":"2005","unstructured":"Kujoth, G. C. et al. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309, 481\u2013484, https:\/\/doi.org\/10.1126\/science.1112125 (2005).","journal-title":"Science"},{"key":"58385_CR8","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s11357-010-9175-3","volume":"33","author":"SM Botter","year":"2011","unstructured":"Botter, S. M. et al. Analysis of osteoarthritis in a mouse model of the progeroid human DNA repair syndrome trichothiodystrophy. Age 33, 247\u2013260, https:\/\/doi.org\/10.1007\/s11357-010-9175-3 (2011).","journal-title":"Age"},{"issue":"Suppl 3","key":"58385_CR9","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.1016\/j.joca.2010.05.025","volume":"18","author":"SS Glasson","year":"2010","unstructured":"Glasson, S. S., Chambers, M. G., Van Den Berg, W. B. & Little, C. B. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse. 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Nature medicine 19, 704\u2013712, https:\/\/doi.org\/10.1038\/nm.3143 (2013).","journal-title":"Nature medicine"},{"key":"58385_CR16","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.joca.2010.01.004","volume":"18","author":"F Intema","year":"2010","unstructured":"Intema, F. et al. In early OA, thinning of the subchondral plate is directly related to cartilage damage: results from a canine ACLT-meniscectomy model. 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