Metformin improves implant osseointegration in type 2 diabetic rats through inhibition high mobility group box 1 and receptor for advanced glycation end product / 中华内分泌代谢杂志

ABSTRACT

Objective:To investigate the effects of metformin on the expression of high mobility group box 1 (HMGB1) and receptor for advanced glycation end product(RAGE) around implants in type 2 diabetic rats and underlying mechanism on bone bonding. To investigate the effect of metformin on osseointegration in non-diabetic rats.Methods:Forty male SD rats aged 6 to 8 weeks were randomly divided into 4 groups by random number table with 10 rats each normal group (T0 group), normal+ metformin group (T1 group), diabetic group (T2 group), and diabetic+ metformin group (T3 group). After type 2 diabetes model was established in T2 and T3 groups, pure titanium implants were implanted in bilateral tibial epiphyseal of all rats. On the same day, T1 and T3 groups were given 300 mg·kg -1·d -1 metformin, and other groups were gavaged with the same amount of normal saline. At the 4th and 8th week after surgery, 5 rats in each group were randomly sacrificed, and bone structure was examined using HE staining and micro-computed tomography (micro-CT). The expression of related factors was detected with immunohistochemistry and enzyme linked immunosorbent assay. Results:At the 4th and 8th week after surgery, the trabecular bone structure, new bone formation quality, and bone microparameters in T3 group were better than those in T2 group. Compared with T2 group, the expression of HMGB1 and RAGE was decreased, the content of osteocalcin was increased, and the expression of tumor necrosis factor-α was decreased (all P<0.01). 4 weeks after operation, bone volume/tissue volume and trabecular number in T1 group was higher than that in T0 group [(0.569±0.013)% vs (0.523±0.030)%, P=0.014; (1.695±0.059)/mm vs (1.569±0.050)/mm, P=0.007]. 8 weeks after operation, trabecular number in T1 group was higher than that in T0 group [(2.324±0.337)/mm vs (1.882±0.057)/mm, P=0.042]. Compared with T0 group, the content of RAGE in T1 group was significantly decreased [(35.49±2.77)ng/L vs (44.92±7.99)ng/L, P=0.005]. The osteocalcin content in T1 group was significantly higher than that in T0 group [(1.32±0.19)ng/L vs (0.89±0.26)ng/L, P=0.001]. Conclusions:Metformin can reduce the expression of HMGB1 and RAGE in type 2 diabetic rats, which may be one of the mechanisms promoting implant bone binding. Metformin has bone protective effect on non-diabetic rats.