Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype in mice
Osteoporosis is a systemic metabolic skeletal disease characterized by low bone mass and strength associated with fragility fractures. Oxidative stress, which results from elevated intracellular reactive oxygen species (ROS) and arises in the aging organism, is considered one of the critical factors...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2022-05-01
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| Series: | Disease Models & Mechanisms |
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| Online Access: | http://dmm.biologists.org/content/15/5/dmm049392 |
| _version_ | 1818212737162936320 |
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| author | Astrid M. Schoppa Xiangxu Chen Jan-Moritz Ramge Anna Vikman Verena Fischer Melanie Haffner-Luntzer Jana Riegger Jan Tuckermann Karin Scharffetter-Kochanek Anita Ignatius |
| author_facet | Astrid M. Schoppa Xiangxu Chen Jan-Moritz Ramge Anna Vikman Verena Fischer Melanie Haffner-Luntzer Jana Riegger Jan Tuckermann Karin Scharffetter-Kochanek Anita Ignatius |
| author_sort | Astrid M. Schoppa |
| collection | DOAJ |
| description | Osteoporosis is a systemic metabolic skeletal disease characterized by low bone mass and strength associated with fragility fractures. 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−) 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. |
| first_indexed | 2024-12-12T05:53:09Z |
| format | Article |
| id | doaj.art-c8aec182ecca4e369874df7f5a60cafd |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-12T05:53:09Z |
| publishDate | 2022-05-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-c8aec182ecca4e369874df7f5a60cafd2022-12-22T00:35:37ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112022-05-0115510.1242/dmm.049392049392Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype in miceAstrid M. Schoppa0Xiangxu Chen1Jan-Moritz Ramge2Anna Vikman3Verena Fischer4Melanie Haffner-Luntzer5Jana Riegger6Jan Tuckermann7Karin Scharffetter-Kochanek8Anita Ignatius9 Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany Department of Orthopedics, Division for Biochemistry of Joint and Connective Tissue Diseases, Ulm University Medical Center, 89081 Ulm, Germany Institute of Comparative Molecular Endocrinology, Ulm University, 89081 Ulm, Germany Department of Dermatology and Allergic Diseases, Ulm University Medical Center, 89081 Ulm, Germany Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, 89081 Ulm, Germany Osteoporosis is a systemic metabolic skeletal disease characterized by low bone mass and strength associated with fragility fractures. 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−) 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.http://dmm.biologists.org/content/15/5/dmm049392skeletal agingosteoporosismitochondrial dysfunctionreactive oxygen speciessenescence |
| spellingShingle | Astrid M. Schoppa Xiangxu Chen Jan-Moritz Ramge Anna Vikman Verena Fischer Melanie Haffner-Luntzer Jana Riegger Jan Tuckermann Karin Scharffetter-Kochanek Anita Ignatius Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype in mice Disease Models & Mechanisms skeletal aging osteoporosis mitochondrial dysfunction reactive oxygen species senescence |
| title | Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype in mice |
| title_full | Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype in mice |
| title_fullStr | Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype in mice |
| title_full_unstemmed | Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype in mice |
| title_short | Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype in mice |
| title_sort | osteoblast lineage sod2 deficiency leads to an osteoporosis like phenotype in mice |
| topic | skeletal aging osteoporosis mitochondrial dysfunction reactive oxygen species senescence |
| url | http://dmm.biologists.org/content/15/5/dmm049392 |
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