| Objective To investigate the effects and possible mechanisms of Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, on bone mass and biomechanical properties of vertebral body after calcium phosphate bone cement reinforcement in rats with diabetic osteoporosis (DOP). Methods The DOP rat model was prepared and the fourth lumbar vertebra was strengthened with calcium phosphate bone cement. The rats were randomly divided into control group, semiglutide group (10 nmol/kg/w subcutaneous injection of semiglutide) and metformin group (100mg/kg/d intragastric administration of metformin). After 8 weeks of intervention, serum was collected and fasting blood glucose (FBG), fasting insulin (FIns), triglyceride (TG), total cholesterol (TC), osteocalcin (OC), procollagen typeI N-terminal propeptide (PINP), collagen type I cross-linked C-telopeptide(CTX-I), tartrate-resistant acid phosphatase 5b (TRACP-5b) were detected. Vertebral body was collected and bone mineral density (BMD), trabecular volume fraction (BV/TV), average trabecular thickness (Tb.Th), average trabecular number (Tb.N), trabecular separation (Tb.Sp), maximum load and stiffness, the mRNA and protein expression levels of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), the protein expression of phosphorylated phosphatidylinositol 3 kinase (p-PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase-3β (p-GSK-3β), β-catenin, advanced glycosylation end products (AGEs), nuclear transcription factor-κB receptor ligand (RANKL), nuclear transcription factor-κ (NF-κB) were detected. Results The levels of serum FBG, FIns, TG, TC, CTX-I, TRACP-5b, the level of Tb.Sp, the mRNA expression level of TRAP in vertebrae, the expression levels of TRAP, AGEs, RANL in total protein and NF-κB in in nuclear protein in Semiglutide group and metformin group were lower than those in control group. The levels of serum OC and PINP, vertebral BMD, BV/TV, Tb.N, Tb.Th and the mRNA expression level of ALP, the expression levels of ALP, p-PI3K, p-Akt, p-GSK-3β in total protein and β-catenin in nuclear protein were higher than those in control group (P<0.05). There was no significant difference in serum FBG, FIns, TG and TC between Semiglutide group and metformin group (P>0.05), whereas the other indexes in Semiglutide group were better than those in metformin group (P<0.05). Conclusion GLP-1 receptor agonist Semaglutide significantly improves the bone mass and biomechanical properties of vertebral body after calcium phosphate bone cement reinforcement in DOP rats. The activation of bone formation mediated by the PI3K/AKT/GSK-3β/β-catenin osteogenic differentiation pathway and inhibition of bone resorption mediated by the AGEs/RANKL/NF-κB osteogenic differentiation pathway are possible molecular mechanisms. |