Irbesartan attenuates advanced glycation end products-mediated damage in diabetes-associated osteoporosis through the AGEs/RAGE pathway
| Autor: | Shuang-Li Yang, Hong Chen, Xiaoyun Zhuo, Hua Zhang, Yanzhen Cheng, Ji-Yu Wang, Li Yang, Meng Ye, Li-Tao Wang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Glycation End Products
Advanced Male 0301 basic medicine medicine.medical_specialty Anabolism Receptor for Advanced Glycation End Products Osteoporosis Tetrazoles medicine.disease_cause General Biochemistry Genetics and Molecular Biology Diabetes Complications Mice 03 medical and health sciences Irbesartan Osteogenesis Glycation Internal medicine medicine Animals General Pharmacology Toxicology and Pharmaceutics Cell Proliferation Mice Knockout chemistry.chemical_classification Reactive oxygen species Osteoblasts Chemistry Biphenyl Compounds Cell Differentiation General Medicine medicine.disease Angiotensin II Biomechanical Phenomena 030104 developmental biology Endocrinology Apoptosis Angiotensin II Type 1 Receptor Blockers Oxidative stress Signal Transduction medicine.drug |
| Zdroj: | Life Sciences. 205:184-192 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2018.04.042 |
| Popis: | Aims Diabetes-associated osteoporosis is mainly caused by the formation and accumulation of advanced glycation end products (AGEs). Angiotensin II type 1 receptor blocker (ARB) has anabolic bone effects on the physicochemical properties of the bone in diabetes. We hypothesized that ARB could inhibit AGEs-induced deleterious effects. Main methods In this study, we chose seven-week-old Leprdb/Lepr+ (db/+) and Leprdb/Leprdb (db/db) mice. After 12 week intervention by irbesartan, the microarchitecture and mechanical strength of the bone of seven-week-old db/db mice were investigated systematically. Meanwhile, the molecular mechanisms of the osteoblasts were analyzed, after AGEs or irbesartan were added to the culture. Also, intracellular formation of reactive oxygen species (ROS) was measured with DCF fluorescence. Key foundings Results showed that 12-week irbesartan treatment could dramatically improve trabecular bone microarchitecture through increasing BV/TV (p = 0.003, +46.7%), Tb.N (p = 0.020, +52.0%), and decreasing that of Tb.Sp (p = 0.005, −21.2%) and SMI (p = 0.007, −26.4%), comparing with the db/db group. Irbesartan could also substantially raise biomechanical parameters including max load (p = 0.013, +20.7%), fracture load (p = 0.014, +70.5%), energy absorption (p = 0.019, +99.4%). Besides, it could inhibit AGEs-induced damage of cell proliferation and osteogenic differentiation of osteoblasts, as well as suppressing the activation of apoptosis caused by AGEs. Moreover, co-incubation with irbesartan could prevent the AGEs-induced increase of intracellular oxidative stress and RAGE expression in osteoblasts. Significance In conclusion, this study suggested that irbesartan might play a protective role in diabetes-related bone damages by blocking the deleterious effects of AGEs/RAGE-mediated oxidative stress. This may provide a revolutionary benefits to therapy with irbesartan on diabetic osteoporosis. |
| Databáze: | OpenAIRE |
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