@article{ATM25885,
author = {Li-Hua Ni and Ri-Ning Tang and Cheng Yuan and Kai-Yun Song and Li-Ting Wang and Xiao-Chen Wang and Yu-Xia Zhang and Xiao-Liang Zhang and Dong-Dong Zhu and Bi-Cheng Liu},
title = {FK506 prevented bone loss in streptozotocin-induced diabetic rats via enhancing osteogenesis and inhibiting adipogenesis},
journal = {Annals of Translational Medicine},
volume = {7},
number = {12},
year = {2019},
keywords = {},
abstract = {Background: Type 1 diabetes mellitus (DM) is associated with severe osteoporosis, which is still a great challenge in the clinic. This work aimed to investigate the skeletal effects of FK506 in a rat model of streptozocin induced type 1 DM.
Methods: Rats were divided into three groups: control (CTL), DM rats and DM rats treated with FK506. Dual energy X-ray absorption, micro-computed tomography, bone mechanics and bone histology were used for skeletal analysis. Bone marrow adipocytes infiltrations were detected by oil red O stain and H&E stain. In addition, the protein expression of adipocyte-specific makers (PPAR-γ, C/EBP-αβ), osteoblast-specific markers (Runx2, Osterix) and nuclear translocation of β-catenin in femurs were determined by western blot.
Results: In the study, bone mineral density of femurs and lumbar vertebras in diabetic rats were increased after FK506 administration. FK506 treatment resulted in higher cancellous bone volume but had no significant effect on cortical bones in diabetic rats. The ultimate force and work to failure were increased in DM+FK506 group, while they were reduced in the DM group. Compared with the CTL, the infiltration of bone marrow adipocytes was significantly increased in the DM group, which was reduced after the treatment of FK506. Besides, the expression levels of Runx2 and Osterix were up-regulated, and that of PPAR-γ and C/EBP-α were down-regulated in diabetic rats after FK506 treatment. In addition, the nuclear translocation of β-catenin protein levels were increased in diabetic rats after the treatment of FK506.
Conclusions: Our study indicated that FK506 could alleviate bone loss in diabetic rats. This effects could be due to the results of enhancing osteogenesis and inhibiting adipogenesis, which might be regulated by activation the nuclear translocation of β-catenin.},
issn = {2305-5847}, url = {https://atm.amegroups.org/article/view/25885}
}