Enhanced SIRT3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitus
Abstract Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus (T2DM), which is characterized by suppressed osteoblast function and disrupted bone microarchitecture. In this study, we utilized male C57BL/6 J mice to investigate the role...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-03-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-024-00399-5 |
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| author | Yansi Xian Bin Liu Tao Shen Lin Yang Rui Peng Hongdou Shen Xueying An Yutian Wang Yu Ben Qing Jiang Baosheng Guo |
| author_facet | Yansi Xian Bin Liu Tao Shen Lin Yang Rui Peng Hongdou Shen Xueying An Yutian Wang Yu Ben Qing Jiang Baosheng Guo |
| author_sort | Yansi Xian |
| collection | DOAJ |
| description | Abstract Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus (T2DM), which is characterized by suppressed osteoblast function and disrupted bone microarchitecture. In this study, we utilized male C57BL/6 J mice to investigate the role of SIRT3 in T2DM. Decreased SIRT3 expression and impaired mitochondrial quality control mechanism are observed in both in vitro and in vivo models of T2DM. Mechanistically, SIRT3 suppression results in hyperacetylation of FOXO3, hindering the activation of the PINK1/PRKN mediated mitophagy pathway and resulting in accumulation of dysfunctional mitochondria. Genetical overexpression or pharmacological activation of SIRT3 restores deacetylation status of FOXO3, thus facilitating mitophagy and ameliorating osteogenic impairment in T2DM. Collectively, our findings highlight the fundamental regulatory function of SIRT3 in mitochondrial quality control, crucial for maintaining bone homeostasis in T2DM. These insights not only enhance our understanding of the molecular mechanisms underlying diabetic osteoporosis but also identify SIRT3 as a promising therapeutic target for diabetic osteoporosis. |
| format | Article |
| id | doaj-art-c9ca80fff9314c8c9704a5aecb36d126 |
| institution | DOAJ |
| issn | 2095-6231 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj-art-c9ca80fff9314c8c9704a5aecb36d1262025-08-20T03:05:52ZengNature Publishing GroupBone Research2095-62312025-03-0113111610.1038/s41413-024-00399-5Enhanced SIRT3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitusYansi Xian0Bin Liu1Tao Shen2Lin Yang3Rui Peng4Hongdou Shen5Xueying An6Yutian Wang7Yu Ben8Qing Jiang9Baosheng Guo10Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityAbstract Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus (T2DM), which is characterized by suppressed osteoblast function and disrupted bone microarchitecture. In this study, we utilized male C57BL/6 J mice to investigate the role of SIRT3 in T2DM. Decreased SIRT3 expression and impaired mitochondrial quality control mechanism are observed in both in vitro and in vivo models of T2DM. Mechanistically, SIRT3 suppression results in hyperacetylation of FOXO3, hindering the activation of the PINK1/PRKN mediated mitophagy pathway and resulting in accumulation of dysfunctional mitochondria. Genetical overexpression or pharmacological activation of SIRT3 restores deacetylation status of FOXO3, thus facilitating mitophagy and ameliorating osteogenic impairment in T2DM. Collectively, our findings highlight the fundamental regulatory function of SIRT3 in mitochondrial quality control, crucial for maintaining bone homeostasis in T2DM. These insights not only enhance our understanding of the molecular mechanisms underlying diabetic osteoporosis but also identify SIRT3 as a promising therapeutic target for diabetic osteoporosis.https://doi.org/10.1038/s41413-024-00399-5 |
| spellingShingle | Yansi Xian Bin Liu Tao Shen Lin Yang Rui Peng Hongdou Shen Xueying An Yutian Wang Yu Ben Qing Jiang Baosheng Guo Enhanced SIRT3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitus Bone Research |
| title | Enhanced SIRT3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitus |
| title_full | Enhanced SIRT3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitus |
| title_fullStr | Enhanced SIRT3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitus |
| title_full_unstemmed | Enhanced SIRT3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitus |
| title_short | Enhanced SIRT3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitus |
| title_sort | enhanced sirt3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitus |
| url | https://doi.org/10.1038/s41413-024-00399-5 |
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