Programa de Pós-Graduação em Odontologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS 90619-900, Brazil; Centro de Pesquisa em Toxicologia e Farmacologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS 90619-900, Brazil.
Centro de Pesquisa em Toxicologia e Farmacologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS 90619-900, Brazil.
Life Sci. 2020 Dec 15;263:118593. doi: 10.1016/j.lfs.2020.118593. Epub 2020 Oct 15.
This study set forth a question: are there any differences in bone responses to insulin and/or vitamin D3 treatment in female and male type 1 diabetic (T1D) mice?
To address this issue, a non-critical sized femur defect was created in streptozotocin (STZ)-T1D mice. Control non-diabetic and T1D female and male mice received: saline; vitamin D3; insulin; or vitamin D3 plus insulin, for 21 days.
Female and male T1D mice showed impaired bone healing, as indicated by histological and micro-computed tomography (micro-CT) analysis. Vitamin D3 or insulin improved the bone regeneration in T1D mice, irrespective of sex. Vitamin D3 plus insulin did not exhibit any additional effects. There were no differences regarding the numbers of TRAP-stained osteoclasts in either evaluated groups. The osteoblast-related gene osterix was upregulated in vitamin D3-treated male T1D mice, as revealed by RT-qPCR. Female T1D mice treated with vitamin D3, insulin, or vitamin D3 plus insulin presented an increased expression of insulin growth factor-1 (IGF-1) mRNA. Conversely, IGF-1 mRNA levels were reduced by the same treatments in male TD1 mice.
Altogether, the results suggested that T1D similarly delayed the osseous healing in female and male mice, with beneficial effects for either vitamin D3 or insulin in T1D mice of both sexes. However, data indicated marked sex differences regarding the expression of genes implicated in bone formation, in T1D mice treated with vitamin D3 and/or insulin.
本研究提出了一个问题：在雌性和雄性 1 型糖尿病（T1D）小鼠中，胰岛素和/或维生素 D3 治疗对骨骼的反应是否存在差异？
为了解决这个问题，在链脲佐菌素（STZ）-T1D 小鼠中创建了一个非临界大小的股骨缺损。对照非糖尿病和 T1D 雌性和雄性小鼠接受以下治疗：生理盐水；维生素 D3；胰岛素；或维生素 D3 加胰岛素，共 21 天。
雌性和雄性 T1D 小鼠的骨愈合受损，组织学和微计算机断层扫描（micro-CT）分析表明。维生素 D3 或胰岛素改善了 T1D 小鼠的骨再生，与性别无关。维生素 D3 加胰岛素没有表现出任何额外的效果。在评估的两组中，TRAP 染色破骨细胞的数量没有差异。RT-qPCR 显示，雄性 T1D 小鼠中维生素 D3 处理上调了成骨相关基因osterix。用维生素 D3、胰岛素或维生素 D3 加胰岛素治疗的雌性 T1D 小鼠，胰岛素生长因子-1（IGF-1）mRNA 的表达增加。相反，相同的治疗方法降低了雄性 TD1 小鼠中 IGF-1 mRNA 的水平。
总的来说，结果表明 T1D 同样延迟了雌性和雄性小鼠的骨骼愈合，维生素 D3 或胰岛素对两性 T1D 小鼠均有益。然而，数据表明，在用维生素 D3 和/或胰岛素治疗的 T1D 小鼠中，与骨形成相关的基因表达存在明显的性别差异。
