title: Effects of angiotensin II type 1 receptor blocker on bones in mice with type 1 diabetes induced by streptozotocin.
abstract: BACKGROUND
  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 bones in diabetic mice.
  
  
  METHODS
  Bone histomorphology was detected by H&E staining, Safranin O staining and X-ray radiography. Micro-CT was performed for the analysis of bone parameters. Gene and protein expression were determined by RT-PCR and immunoblotting.
  
  
  RESULTS
  Type 1 diabetic mice displayed osteopenia phenotype, and losartan treatment had no osteoprotective effects on diabetic mice as shown by the reduction of bone mineral density and microarchitectural parameters at the proximal metaphysis of the tibia. The mRNA expression of AGT, renin receptor and ACE, and protein expression of renin and AT1R 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, and reduced the expression of AT2R receptor as compared to those of diabetic mice.
  
  
  CONCLUSIONS
  Local bone RAS functionally played a role in the development of type 1 diabetic osteoporosis, and losartan had no bone-sparing function in diabetes mice because of enhance skeletal RAS activity.
authors.affiliation: Center for Systems Biomedical Sciences, University of Shanghai for Science and Technology, People's Republic of China Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, People's Republic of China School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, People's Republic of China bcmswong@polyu.edu.hk medicineyan@yahoo.com.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Systems Biomedical Sciences, University of Shanghai for Science and Technology, People's Republic of China School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, People's Republic of China.
authors.forename: Teng-Yue
authors.initials: TY
authors.lastname: Diao
authors.affiliation: Center for Systems Biomedical Sciences, University of Shanghai for Science and Technology, People's Republic of China School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, People's Republic of China.
authors.forename: Sa-Sa
authors.initials: SS
authors.lastname: Gu
authors.affiliation: Center for Systems Biomedical Sciences, University of Shanghai for Science and Technology, People's Republic of China.
authors.forename: Shu-Yan
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Center for Systems Biomedical Sciences, University of Shanghai for Science and Technology, People's Republic of China School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, People's Republic of China.
authors.forename: Yoseph A
authors.initials: YA
authors.lastname: Gebru
authors.affiliation: School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiology, The Norman Bethune First Hospital of Jilin University, People's Republic of China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Center for Systems Biomedical Sciences, University of Shanghai for Science and Technology, People's Republic of China.
authors.forename: Shu
authors.initials: S
authors.lastname: Ran
authors.affiliation: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, People's Republic of China.
authors.forename: Man-Sau
authors.initials: MS
authors.lastname: Wong
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology* / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000473:pathology* / Q000652:urine; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D008297:Male; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D013311:Streptozocin; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D055114:X-Ray Microtomography
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D012333:RNA, Messenger; D013311:Streptozocin
keywords: Bone; losartan; osteoporosis; renin-angiotensin system; streptozotocin