Daphnetin Alleviates Senile and Disuse Osteoporosis by Distinct Modulations of Bone Formation and Resorption
Senile and disuse osteoporosis have distinct bone turnover status and lack effective treatments. In this study, senescence-accelerated mouse prone 8 (SAMP8) and hindlimb unloading mouse models were used to explore the protective effects of daphnetin on these two types of osteoporosis, and primary os...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/12/2365 |
| _version_ | 1827642108546121728 |
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| author | Jing Gao Zhen Wang Peipei Gao Qiang Fan Tiantian Zhang Li Cui Liujia Shi Zhongbo Liu Zhiwei Yang Langchong He Chunyan Wang Yinghui Li Lina Qu Jiankang Liu Jiangang Long |
| author_facet | Jing Gao Zhen Wang Peipei Gao Qiang Fan Tiantian Zhang Li Cui Liujia Shi Zhongbo Liu Zhiwei Yang Langchong He Chunyan Wang Yinghui Li Lina Qu Jiankang Liu Jiangang Long |
| author_sort | Jing Gao |
| collection | DOAJ |
| description | Senile and disuse osteoporosis have distinct bone turnover status and lack effective treatments. In this study, senescence-accelerated mouse prone 8 (SAMP8) and hindlimb unloading mouse models were used to explore the protective effects of daphnetin on these two types of osteoporosis, and primary osteoblasts and bone marrow monocyte-derived osteoclasts, as well as pre-osteoblast MC3T3-E1, and osteoclast precursor RAW264.7 cells were used to investigate the underlying mechanisms. The results showed that daphnetin administration effectively improved bone remodeling in both senile and disuse osteoporosis, but with different mechanisms. In senile osteoporosis with low bone turnover, daphnetin inhibited NOX2-mediated ROS production in osteoblasts, resulting in accelerated osteogenic differentiation and bone formation, while in disuse osteoporosis with high bone turnover, daphnetin restored SIRT3 expression, maintained mitochondrial homeostasis, and additionally upregulated SOD2 to eliminate ROS in osteoclasts, resulting in attenuation of osteoclast differentiation and bone resorption. These findings illuminated that daphnetin has promising potential for the prevention and treatment of senile and disuse osteoporosis. The different mechanisms may provide clues and basis for targeted prevention and treatment of osteoporosis according to distinct bone turnover status. |
| first_indexed | 2024-03-09T17:23:58Z |
| format | Article |
| id | doaj.art-5fe68cf09530446f833bc324f03e2302 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T17:23:58Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-5fe68cf09530446f833bc324f03e23022023-11-24T12:56:49ZengMDPI AGAntioxidants2076-39212022-11-011112236510.3390/antiox11122365Daphnetin Alleviates Senile and Disuse Osteoporosis by Distinct Modulations of Bone Formation and ResorptionJing Gao0Zhen Wang1Peipei Gao2Qiang Fan3Tiantian Zhang4Li Cui5Liujia Shi6Zhongbo Liu7Zhiwei Yang8Langchong He9Chunyan Wang10Yinghui Li11Lina Qu12Jiankang Liu13Jiangang Long14Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, ChinaCenter for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, ChinaCenter for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, ChinaCenter for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, ChinaCenter for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, ChinaCenter for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, ChinaDepartment of Cellular and Molecular Biology, State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, ChinaKey Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Laboratory Center of Stomatology, College of Stomatology, Xi’an Jiaotong University, Xi’an 710004, ChinaSchool of Physics, Xi’an Jiaotong University, Xi’an 710049, ChinaSchool of Pharmacy, Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Cellular and Molecular Biology, State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, ChinaDepartment of Cellular and Molecular Biology, State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, ChinaDepartment of Cellular and Molecular Biology, State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, ChinaSchool of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, ChinaCenter for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, ChinaSenile and disuse osteoporosis have distinct bone turnover status and lack effective treatments. In this study, senescence-accelerated mouse prone 8 (SAMP8) and hindlimb unloading mouse models were used to explore the protective effects of daphnetin on these two types of osteoporosis, and primary osteoblasts and bone marrow monocyte-derived osteoclasts, as well as pre-osteoblast MC3T3-E1, and osteoclast precursor RAW264.7 cells were used to investigate the underlying mechanisms. The results showed that daphnetin administration effectively improved bone remodeling in both senile and disuse osteoporosis, but with different mechanisms. In senile osteoporosis with low bone turnover, daphnetin inhibited NOX2-mediated ROS production in osteoblasts, resulting in accelerated osteogenic differentiation and bone formation, while in disuse osteoporosis with high bone turnover, daphnetin restored SIRT3 expression, maintained mitochondrial homeostasis, and additionally upregulated SOD2 to eliminate ROS in osteoclasts, resulting in attenuation of osteoclast differentiation and bone resorption. These findings illuminated that daphnetin has promising potential for the prevention and treatment of senile and disuse osteoporosis. The different mechanisms may provide clues and basis for targeted prevention and treatment of osteoporosis according to distinct bone turnover status.https://www.mdpi.com/2076-3921/11/12/2365daphnetinsenile osteoporosisdisuse osteoporosisosteoblastosteoclastNADPH oxidase |
| spellingShingle | Jing Gao Zhen Wang Peipei Gao Qiang Fan Tiantian Zhang Li Cui Liujia Shi Zhongbo Liu Zhiwei Yang Langchong He Chunyan Wang Yinghui Li Lina Qu Jiankang Liu Jiangang Long Daphnetin Alleviates Senile and Disuse Osteoporosis by Distinct Modulations of Bone Formation and Resorption Antioxidants daphnetin senile osteoporosis disuse osteoporosis osteoblast osteoclast NADPH oxidase |
| title | Daphnetin Alleviates Senile and Disuse Osteoporosis by Distinct Modulations of Bone Formation and Resorption |
| title_full | Daphnetin Alleviates Senile and Disuse Osteoporosis by Distinct Modulations of Bone Formation and Resorption |
| title_fullStr | Daphnetin Alleviates Senile and Disuse Osteoporosis by Distinct Modulations of Bone Formation and Resorption |
| title_full_unstemmed | Daphnetin Alleviates Senile and Disuse Osteoporosis by Distinct Modulations of Bone Formation and Resorption |
| title_short | Daphnetin Alleviates Senile and Disuse Osteoporosis by Distinct Modulations of Bone Formation and Resorption |
| title_sort | daphnetin alleviates senile and disuse osteoporosis by distinct modulations of bone formation and resorption |
| topic | daphnetin senile osteoporosis disuse osteoporosis osteoblast osteoclast NADPH oxidase |
| url | https://www.mdpi.com/2076-3921/11/12/2365 |
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