Daphnetin Alleviates Senile and Disuse Osteoporosis by Distinct Modulations of Bone Formation and Resorption
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
Affiliations
Jing Gao
Center 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, China
Zhen Wang
Center 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, China
Peipei Gao
Center 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, China
Qiang Fan
Center 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, China
Tiantian Zhang
Center 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, China
Li Cui
Center 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, China
Liujia Shi
Department of Cellular and Molecular Biology, State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China
Zhongbo Liu
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Laboratory Center of Stomatology, College of Stomatology, Xi’an Jiaotong University, Xi’an 710004, China
Zhiwei Yang
School of Physics, Xi’an Jiaotong University, Xi’an 710049, China
Langchong He
School of Pharmacy, Xi’an Jiaotong University, Xi’an 710061, China
Chunyan Wang
Department of Cellular and Molecular Biology, State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China
Yinghui Li
Department of Cellular and Molecular Biology, State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China
Lina Qu
Department of Cellular and Molecular Biology, State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China
Jiankang Liu
School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, China
Jiangang Long
Center 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, China
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.
