Cell Reports Medicine (Sep 2024)
Advanced glycation end products mediate biomineralization disorder in diabetic bone disease
- Qianmin Gao,
- Yingying Jiang,
- Dongyang Zhou,
- Guangfeng Li,
- Yafei Han,
- Jingzhi Yang,
- Ke Xu,
- Yingying Jing,
- Long Bai,
- Zhen Geng,
- Hao Zhang,
- Guangyin Zhou,
- Mengru Zhu,
- Ning Ji,
- Ruina Han,
- Yuanwei Zhang,
- Zuhao Li,
- Chuandong Wang,
- Yan Hu,
- Hao Shen,
- Guangchao Wang,
- Zhongmin Shi,
- Qinglin Han,
- Xiao Chen,
- Jiacan Su
Affiliations
- Qianmin Gao
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Yingying Jiang
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China; Corresponding author
- Dongyang Zhou
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Guangfeng Li
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Yafei Han
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Jingzhi Yang
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Ke Xu
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Yingying Jing
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Long Bai
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Zhen Geng
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Hao Zhang
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China; Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
- Guangyin Zhou
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Mengru Zhu
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Ning Ji
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Ruina Han
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China
- Yuanwei Zhang
- Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
- Zuhao Li
- Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
- Chuandong Wang
- Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
- Yan Hu
- Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
- Hao Shen
- Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
- Guangchao Wang
- Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
- Zhongmin Shi
- Department of Orthopedics, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, P.R. China
- Qinglin Han
- Orthopaedic Department, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China; Corresponding author
- Xiao Chen
- Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China; Corresponding author
- Jiacan Su
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, P.R. China; Organoid Research Center, Shanghai University, Shanghai 200444, P.R. China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, P.R. China; Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China; Corresponding author
- Journal volume & issue
-
Vol. 5,
no. 9
p. 101694
Abstract
Summary: Patients with diabetes often experience fragile fractures despite normal or higher bone mineral density (BMD), a phenomenon termed the diabetic bone paradox (DBP). The pathogenesis and therapeutics opinions for diabetic bone disease (DBD) are not fully explored. In this study, we utilize two preclinical diabetic models, the leptin receptor-deficient db/db mice (DB) mouse model and the streptozotocin-induced diabetes (STZ) mouse model. These models demonstrate higher BMD and lower mechanical strength, mirroring clinical observations in diabetic patients. Advanced glycation end products (AGEs) accumulate in diabetic bones, causing higher non-enzymatic crosslinking within collagen fibrils. This inhibits intrafibrillar mineralization and leads to disordered mineral deposition on collagen fibrils, ultimately reducing bone strength. Guanidines, inhibiting AGE formation, significantly improve the microstructure and biomechanical strength of diabetic bone and enhance bone fracture healing. Therefore, targeting AGEs may offer a strategy to regulate bone mineralization and microstructure, potentially preventing the onset of DBD.
