Advanced glycation end products mediate biomineralization disorder in diabetic bone disease
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.
Authors
- Zuhao Li (ORCID: https://orcid.org/0000-0002-3752-7899)
- Zhongmin Shi (ORCID: https://orcid.org/0000-0002-2467-8735)
- Yan Hu (ORCID: https://orcid.org/0000-0003-3269-4505)
- Yingying Jing (ORCID: https://orcid.org/0000-0001-6103-8430)
- Yuanwei Zhang
- Yingying Jiang (ORCID: https://orcid.org/0000-0002-0788-8546)
- Mengru Zhu
- Guangfeng Li (ORCID: https://orcid.org/0000-0003-1589-7618)
- Dongyang Zhou (ORCID: https://orcid.org/0000-0001-8895-9707)
- Qianmin Gao (ORCID: https://orcid.org/0000-0001-5907-3325)
- Ruina Han
- Ke Xu (ORCID: https://orcid.org/0000-0002-3942-2767)
- Hao Shen (ORCID: https://orcid.org/0000-0002-4688-9146)
- Ning Ji (ORCID: https://orcid.org/0000-0001-7702-1537)
- Bai Long (ORCID: https://orcid.org/0009-0008-6178-2989)
- Guangchao Wang (ORCID: https://orcid.org/0000-0003-4285-7144)
- Chuandong Wang (ORCID: https://orcid.org/0000-0003-0528-4105)
- Qinglin Han
- Guangyin Zhou (ORCID: https://orcid.org/0009-0007-5795-8470)
- Jiacan Su (ORCID: https://orcid.org/0000-0001-7080-263X)
- Xiao Chen (ORCID: https://orcid.org/0009-0009-3435-7271)
- Yafei Han
- Zhen Geng
- Jingzhi Yang (ORCID: https://orcid.org/0000-0003-4956-6104)
- Hao Zhang (ORCID: https://orcid.org/0009-0006-9483-834X)
Institutions
- Shanghai University (CN)
- Nantong University (CN)
- XinHua Hospital (CN)
- Affiliated Hospital of Nantong University (CN)
- Shanghai Sixth People's Hospital (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2024-08-23
- DOI
- https://doi.org/10.1016/j.xcrm.2024.101694
- Citations
- 52
- Primary Topic
- Bone and Dental Protein Studies
- Type
- article
- Field-Weighted Citation Impact
- 24.45
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Science and Technology Commission of Shanghai Municipality
- Shanghai Hospital Development Center
- Shanghai Rising-Star Program