Abstract
Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2.
Highlights
There is strong evidence indicating that patients with diabetes mellitus type 1 (DM1) have decreased bone mass and are at increased risk of fragility fractures [1,2,3,4,5]
Biomechanical function The mechanical parameters of the control and diabetes groups increased continuously throughout the experimental period; two-way ANOVA revealed that the diabetes group had significantly lower mean values for the bending rigidity, torsional rigidity and destruction torque than the control group Po0.05 (Figure 1)
In the control group at week 1 post-fracture, a moderate staining for Transforming growth factor beta 1 (TGF-b1) was seen in osteogenic cells, fibroblast-like cells, chondrocytes, and osteoblasts in both the subperiosteal bone and the trabecular bone near the endochondral ossification front
Summary
Effect of diabetes mellitus on fracture healing fibular fracture in an alloxan-induced diabetic rat model at 4 weeks post-fracture. The mechanisms of delayed fracture healing in diabetic patients or animal models remain unclear. Transforming growth factor beta 1 (TGF-b1) and bone morphogenetic protein-2 (BMP-2) are two very important factors in the process of bone healing [14,15,16,17,18,19]. Little is known about the expression of TGF-β1 and BMP2 in the bone healing processes of patients with diabetes. Mounted on a combined axial motion and torsional testing jig that was attached to a biaxial material testing machine (MTS 858 Bionix, MTS Systems, USA). Three mechanical testing parameters were measured in both diabetic and control rats. The samples were tested to failure in displacement control at a rate of 15 mm/min using a biaxial material testing machine (MTS 858 Bionix). A torque test was conducted to failure at a rate of 15 mm/min. The bent rigidity, torsional rigidity, and destruction torque were automatically calculated using MTS 858 Bionix software
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