Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats

Authors:
  • RMRufeng Ma
    Rufeng Ma
  • LWLili Wang
    Lili Wang
  • BZBaosheng Zhao
    Baosheng Zhao
  • CLChenyue Liu
    Chenyue Liu
  • HLHaixia Liu
    Haixia Liu
  • RZRuyuan Zhu
    Ruyuan Zhu
  • BCBeibei Chen
    Beibei Chen
  • LLLin Li
    Lin Li
  • DZDandan Zhao
    Dandan Zhao
  • FMFangfang Mo
    Fangfang Mo
  • YLYu Li
    Yu Li
  • JNJianzhao Niu
    Jianzhao Niu
Open Access
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Abstract
Purpose: 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.

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