1. Advanced glycation end products mediate biomineralization disorder in diabetic bone disease.
- Author
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Gao Q, Jiang Y, Zhou D, Li G, Han Y, Yang J, Xu K, Jing Y, Bai L, Geng Z, Zhang H, Zhou G, Zhu M, Ji N, Han R, Zhang Y, Li Z, Wang C, Hu Y, Shen H, Wang G, Shi Z, Han Q, Chen X, and Su J
- Subjects
- Animals, Mice, Biomineralization, Male, Mice, Inbred C57BL, Receptors, Leptin metabolism, Receptors, Leptin genetics, Bone and Bones metabolism, Bone and Bones pathology, Bone Diseases pathology, Bone Diseases metabolism, Disease Models, Animal, Collagen metabolism, Diabetes Complications metabolism, Diabetes Complications pathology, Guanidines pharmacology, Glycation End Products, Advanced metabolism, Diabetes Mellitus, Experimental metabolism, Diabetes Mellitus, Experimental pathology, Diabetes Mellitus, Experimental complications, Bone Density
- Abstract
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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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