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Oxidative stress, which results from elevated intracellular reactive oxygen species (ROS) and arises in the aging organism, is considered one of the critical factors contributing to osteoporosis. Mitochondrial (mt)ROS, as the superoxide anion (O2\u2212) generated during mitochondrial respiration, are eliminated in the young organism by antioxidant defense mechanisms, including superoxide dismutase 2 (SOD2), the expression and activity of which are decreased in aging mesenchymal progenitor cells, accompanied by increased mtROS production. Using a mouse model of osteoblast lineage cells with Sod2 deficiency, we observed significant bone loss in trabecular and cortical bones accompanied by decreased osteoblast activity, increased adipocyte accumulation in the bone marrow and augmented osteoclast activity, suggestive of altered mesenchymal progenitor cell differentiation and osteoclastogenesis. Furthermore, osteoblast senescence was increased. To date, there are only a few studies suggesting a causal association between mtROS and cellular senescence in tissue in vivo. Targeting SOD2 to improve redox homeostasis could represent a potential therapeutic strategy for maintaining bone health during aging.<\/jats:p>","DOI":"10.1242\/dmm.049392","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T10:08:28Z","timestamp":1649412508000},"source":"Crossref","is-referenced-by-count":41,"title":["Osteoblast lineage <i>Sod2<\/i> deficiency leads to an osteoporosis-like phenotype in mice"],"prefix":"10.1242","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3559-7081","authenticated-orcid":false,"given":"Astrid M.","family":"Schoppa","sequence":"first","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6500-6145","authenticated-orcid":false,"given":"Xiangxu","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Moritz","family":"Ramge","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8531-9712","authenticated-orcid":false,"given":"Anna","family":"Vikman","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Haffner-Luntzer","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Riegger","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Division for Biochemistry of Joint and Connective Tissue Diseases, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Tuckermann","sequence":"additional","affiliation":[{"name":"Institute of Comparative Molecular Endocrinology, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Scharffetter-Kochanek","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Ignatius","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,5,13]]},"reference":[{"key":"2022051308290606300_DMM049392C1","doi-asserted-by":"publisher","first-page":"3576","DOI":"10.3390\/ijms20143576","article-title":"Reactive oxygen species in osteoclast differentiation and possible pharmaceutical targets of ROS-mediated osteoclast diseases","volume":"20","author":"Agidigbi","year":"2019","journal-title":"Int. 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