title: Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats.
abstract: OBJECTIVE
  Increasing evidence supported that semaphorin 3A (Sema3A), insulin-like growth factor (IGF)-1 and β-catenin were involved in the development of osteoporosis and diabetes. This study is aimed to evaluate whether Sema3A/IGF-1/β-catenin is directly involved in the alterations of bone microarchitecture and bone strength of diabetic rats.
  
  
  METHODS
  Diabetic rats were induced by streptozotocin and high fat diet exposure. Bone microarchitecture and strength in the femurs were evaluated by micro-CT scanning, three-point bending examination and the stainings of HE, alizarin red S and safranin O/fast green, respectively. The alterations of lumbar spines microarchitecture were also determined by micro-CT scanning. Western blot and immunohistochemical analyses were used to examine the expression of Sema3A, β-catenin, IGF-1, peroxisome proliferator-activated receptor γ (PPARγ) and cathepsin K in rat tibias.
  
  
  RESULTS
  Diabetic rats exhibited decreased trabecular numbers and bone formation, but an increased trabecular separation in the femurs and lumbar spines. Moreover, the increased bone fragility and decreased bone stiffness were evident in the femurs of diabetic rats. Diabetic rats also exhibited a pronounced bone phenotype which manifested by decreased expression of Sema3A, IGF-1 and β-catenin, as well as increased expression of cathepsin K and PPARγ.
  
  
  CONCLUSIONS
  This study suggests that diabetes could perturb bone loss through the Sema3A/IGF-1/β-catenin pathway. Sema3A deficiency in bone may contribute to upregulation of PPARγ and cathepsin K expression, which further disrupts bone remodeling in diabetic rats.
authors.forename: Rufeng
authors.initials: R
authors.lastname: Ma
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Baosheng
authors.initials: B
authors.lastname: Zhao
authors.forename: Chenyue
authors.initials: C
authors.lastname: Liu
authors.forename: Haixia
authors.initials: H
authors.lastname: Liu
authors.forename: Ruyuan
authors.initials: R
authors.lastname: Zhu
authors.forename: Beibei
authors.initials: B
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhao
authors.forename: Fangfang
authors.initials: F
authors.lastname: Mo
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Jianzhao
authors.initials: J
authors.lastname: Niu
authors.forename: Guangjian
authors.initials: G
authors.lastname: Jiang
authors.forename: Min
authors.initials: M
authors.lastname: Fu
authors.forename: Dieter
authors.initials: D
authors.lastname: Bromme
authors.forename: Sihua
authors.initials: S
authors.lastname: Gao
authors.forename: Dongwei
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000502:physiology* / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D059305:Diet, High-Fat; D005260:Female; D005269:Femur / Q000502:physiology; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D040121:Semaphorin-3A / Q000378:metabolism*; D013311:Streptozocin / Q000633:toxicity; D055114:X-Ray Microtomography; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D047495:PPAR gamma; D040121:Semaphorin-3A; D051176:beta Catenin; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I
keywords: Cathepsin K; Diabetic rats; Insulin-like growth factor-1 (IGF); Peroxisome proliferator-activated receptor γ (PPAR γ); Sema3A; β-catenin