Effects of angiotensin II type 1 receptor blocker on bones in mice with type 1 diabetes induced by streptozotocin

Introduction: This study was performed to address the pathological roles of the skeletal renin-angiotensin system (RAS)in type 1 diabetes-induced osteoporosis and the effects of the angiotensin II type 1 receptor blocker losartan on bonesin diabetic mice.Materials and methods: Bone histomorphology was detected by staining, Safranin O staining and X-ray radiography.Micro-CT was performed for the analysis of bone parameters. Gene and protein expression were determined byRT-PCR and immunoblotting.Results: Type 1 diabetic mice displayed osteopenia phenotype, and losartan treatment had no osteoprotective effectson diabetic mice as shown by the reduction of bone mineral density and microarchitectural parameters at the proximalmetaphysis of the tibia. The mRNA expression of AGT, renin receptor and ACE, and protein expression of renin andAT1R were markedly up-regulated in the bones of vehicle-treated diabetic mice compared to those of non-diabetic mice.The treatment with losartan further significantly increased the expression of AGT, renin, angiotensin II and AT1R, andreduced the expression of AT2R receptor as compared to those of diabetic mice.Conclusion: Local bone RAS functionally played a role in the development of type 1 diabetic osteoporosis, and losartanhad no bone-sparing function in diabetes mice because of enhance skeletal RAS activity.