Yan-Zhen Cheng1, Shuang-Li Yang2, Ji-Yu Wang1, Meng Ye3, Xiao-Yun Zhuo1, Li-Tao Wang1, Hong Chen1, Hua Zhang1, Li Yang4. 1. Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, PR China. 2. Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, PR China; Department of Endocrinology, Second Affiliated Hospital of GuiZhou Medical University, Kaili, Guizhou, PR China. 3. Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, PR China; Department of Endocrinology, Affiliated Hospital of GuiZhou Medical University, Guiyang, Guizhou, PR China. 4. Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, PR China. Electronic address: yangli19762009@163.com.
Abstract
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.
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.
Authors: Ye Hongwei; Cao Ruiping; Fang Yingyan; Zhang Guanjun; Hu Jie; Liu Xingyu; Tang Jie; Li Zhenghong; Gao Qin; Hu Junfeng; Zhang Heng Journal: Exp Biol Med (Maywood) Date: 2019-04-26
Authors: Marco Raffaele; Ignazio Barbagallo; Maria Licari; Giuseppe Carota; Giuseppe Sferrazzo; Mariarita Spampinato; Valeria Sorrenti; Luca Vanella Journal: Evid Based Complement Alternat Med Date: 2018-10-17 Impact factor: 2.629
Authors: Ji-Yu Wang; Yan-Zhen Cheng; Shuang-Li Yang; Min An; Hua Zhang; Hong Chen; Li Yang Journal: Front Endocrinol (Lausanne) Date: 2019-11-05 Impact factor: 5.555