title: Local bone interaction between renin-angiotensin system and kallikrein-kinin system in diabetic rat.
abstract: OBJECTIVE
  This study was performed to investigate bone deteriorations and the involvement of skeletal renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) of male rat in response to the hyperglycemia.
  
  
  METHODS
  The biomarkers in serum and urine were measured by ELISA kit, and tibias were taken for the measurement on gene, protein expression and histological analysis, femurs were taken for the measurement on biomechanical parameters and micro-CT.
  
  
  RESULTS
  The DM1 showed the decreased level of osteocalcin, testosterone and FGF-23, and the increased level of serum CTX as compared to those of vehicle group. The H&E staining showed remarkable bone deteriorations, including increased disconnections and separation of trabecular bone among growth plate and joint cartilage in DM1 group. Biomechanically, the maximum load, maximum stress, and strain parameter of DM1 group was significantly lower than control group. Type 1 diabetic mice displayed bone loss shown the reduction of bone volume/total volume, trabecular number, trabecular thickness and bone mineral density. The STZ injection significantly up-regulated mRNA expression of AT1R, AGT, renin, renin-receptor, and ACE, and the expression of AT2R, B1R and B2R were down-regulated in tibia of rat in hyperglycemia group. The protein expression of renin, ACE and Ang II were significantly up-regulated, and AT2R, B1R and B2R were down-regulated in DM1 group.
  
  
  CONCLUSIONS
  The treatment of hyperglycemia was detrimental to bone as compared to the vehicle group, and the underlying mechanism was mediated, at least partially, through down-regulation of KSS activity and up-regulation of RAS activity in local bone.
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Soochow University 1055 Sanxiang Road, Suzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University 1055 Sanxiang Road, Suzhou, China.
authors.forename: Guang-Si
authors.initials: GS
authors.lastname: Shen
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University 1055 Sanxiang Road, Suzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University 1055 Sanxiang Road, Suzhou, China.
authors.forename: Guang-Fei
authors.initials: GF
authors.lastname: Li
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Soochow University 1055 Sanxiang Road, Suzhou, China.
authors.forename: Jun-Kang
authors.initials: JK
authors.lastname: Shen
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University 1055 Sanxiang Road, Suzhou, China.
authors.forename: You-Jia
authors.initials: YJ
authors.lastname: Xu
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Soochow University 1055 Sanxiang Road, Suzhou, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Gong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D000089703:Fibroblast Growth Factor-23; D016234:Kallikrein-Kinin System / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012084:Renin-Angiotensin System / Q000502:physiology*
keywords: Renin-angiotensin system; bone; hyperglycemia; kallikrein-kinin system