Ma Rufeng, Wang Lili, Zhao Baosheng, Liu Chenyue, Liu Haixia, Zhu Ruyuan, Chen Beibei, Li Lin, Zhao Dandan, Mo Fangfang, Li Yu, Niu Jianzhao, Jiang Guangjian, Fu Min, Bromme Dieter, Gao Sihua, Zhang Dongwei
Cell Physiol Biochem. 2017;41(1):55-66. doi: 10.1159/000455936. Epub 2017 Jan 17.
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.
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.
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.
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.
越来越多的证据表明，信号素3A（Sema3A）、胰岛素样生长因子（IGF）-1和β-连环蛋白参与了骨质疏松症和糖尿病的发展。本研究旨在评估Sema3A/IGF-1/β-连环蛋白是否直接参与糖尿病大鼠骨微结构和骨强度的改变。
通过链脲佐菌素和高脂饮食诱导糖尿病大鼠。分别采用显微CT扫描、三点弯曲试验以及HE、茜素红S和番红O/固绿染色评估股骨的骨微结构和强度。还通过显微CT扫描确定腰椎微结构的改变。采用蛋白质印迹法和免疫组织化学分析法检测大鼠胫骨中Sema3A、β-连环蛋白、IGF-1、过氧化物酶体增殖物激活受体γ（PPARγ）和组织蛋白酶K的表达。
糖尿病大鼠股骨和腰椎的骨小梁数量减少、骨形成减少，但骨小梁间距增加。此外，糖尿病大鼠股骨的骨脆性增加和骨硬度降低明显。糖尿病大鼠还表现出明显的骨表型，表现为Sema3A、IGF-1和β-连环蛋白表达降低，以及组织蛋白酶K和PPARγ表达增加。
本研究表明，糖尿病可能通过Sema3A/IGF-1/β-连环蛋白途径扰乱骨质流失。骨中Sema3A缺乏可能导致PPARγ和组织蛋白酶K表达上调，进而进一步破坏糖尿病大鼠的骨重塑。
