Bone regeneration in a mouse model of type 1 diabetes: Influence of sex, vitamin D3, and insulin

Aim: 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? Main methods: 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. Key findings: 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. Significance: 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.