Nature Communications (Oct 2024)
Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity
- Chuanxin Zhong,
- Nanxi Li,
- Shengzheng Wang,
- Dijie Li,
- Zhihua Yang,
- Lin Du,
- Guangxin Huang,
- Haitian Li,
- Wing Sze Yeung,
- Shan He,
- Shuting Ma,
- Zhuqian Wang,
- Hewen Jiang,
- Huarui Zhang,
- Zhanghao Li,
- Xiaoxin Wen,
- Song Xue,
- Xiaohui Tao,
- Haorui Li,
- Duoli Xie,
- Yihao Zhang,
- Zefeng Chen,
- Junqin Wang,
- Jianfeng Yan,
- Zhengming Liang,
- Zongkang Zhang,
- Zhigang Zhong,
- Zeting Wu,
- Chao Wan,
- Chao Liang,
- Luyao Wang,
- Sifan Yu,
- Yuan Ma,
- Yuanyuan Yu,
- Fangfei Li,
- Yang Chen,
- Baoting Zhang,
- Aiping Lyu,
- Fuzeng Ren,
- Hong Zhou,
- Jin Liu,
- Ge Zhang
Affiliations
- Chuanxin Zhong
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Nanxi Li
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Shengzheng Wang
- Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University
- Dijie Li
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Zhihua Yang
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
- Lin Du
- Sports Medicine Center, The First Affiliated Hospital of Shantou University Medical College
- Guangxin Huang
- Department of Joint Surgery, The Third Affiliated Hospital of Southern Medical University, The Third School of Clinical Medicine, Southern Medical University
- Haitian Li
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Wing Sze Yeung
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Shan He
- Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen
- Shuting Ma
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Zhuqian Wang
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Hewen Jiang
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong
- Huarui Zhang
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong
- Zhanghao Li
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Xiaoxin Wen
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Song Xue
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital
- Xiaohui Tao
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Haorui Li
- Sports Medicine Center, The First Affiliated Hospital of Shantou University Medical College
- Duoli Xie
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Yihao Zhang
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Zefeng Chen
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Junqin Wang
- Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen
- Jianfeng Yan
- Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen
- Zhengming Liang
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Zongkang Zhang
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong
- Zhigang Zhong
- Sports Medicine Center, The First Affiliated Hospital of Shantou University Medical College
- Zeting Wu
- International Medical Service Center, The First Affiliated Hospital of Shantou University Medical College
- Chao Wan
- Key Laboratory of Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong
- Chao Liang
- Department of Biology, Southern University of Science and Technology
- Luyao Wang
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Sifan Yu
- Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery
- Yuan Ma
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Yuanyuan Yu
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Fangfei Li
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Yang Chen
- Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences
- Baoting Zhang
- Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery
- Aiping Lyu
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Fuzeng Ren
- Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen
- Hong Zhou
- Bone Research Program, ANZAC Research Institute, The University of Sydney
- Jin Liu
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- Ge Zhang
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
- DOI
- https://doi.org/10.1038/s41467-024-52965-4
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 18
Abstract
Abstract Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Recent findings suggest that disrupting skeletal GC signaling prevents bone loss and alleviates metabolic disorders in high-fat diet (HFD)-fed obese mice, underpinning the neglected contribution of skeletal GC action to obesity and related bone loss. Here, we show that the elevated expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the enzyme driving local GC activation, and GC signaling in osteoblasts, are associated with bone loss and obesity in HFD-fed male mice. Osteoblast-specific 11β-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11β-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11β-HSD1 by using bone-targeted 11β-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11β-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity.