Effects of liraglutide on bone metabolism and Wnt pathway in type 2 diabetic rats with osteoporosis

Abstract

Objective To study the effects of liraglutide on bone metabolism and Wnt pathway in type 2 diabetic osteoporosis rats. Methods SD rats were randomly divided into control group, model group and liraglutide group. The latter two groups were fed with high-fat and high-sugar diet and intraperitoneally injected with low-dose streptozotocin to establish type 2 diabetic model. Liraglutide group was subcutaneously injected with 0.6 mg/kg/d liraglutide for 8 weeks. Bone mineral density, calcium and phosphorus content, the expression of Wnt pathway molecule [Wnt3a, low density lipoprotein receptor-related protein 5 (LRP5) , β-catenin] and the contents of bone metabolism indicators [ALP, osteocalcin (OC) , osteoprotegerin (OPG) , receptor activator of nuclear factor-κ B ligand (RANKL) , tartrate-resistant acid phosphatase (TrACP) , cross-linked carboxy-terminal telopeptide of type I collagen (CTX-1) ] in serum were determined. Results The tibial bone mineral density[left (0.158±0.024) vs (0.232±0.041) g/cm2, right (0.152±0.027) vs (0.219±0.038) g/cm2, P<0.05) , the content of calcium and phosphorus [ (5.12±0.58) vs (5.93±0.74) mol/g, (2.93±0.41) vs (3.84±0.56) mol/g, P<0.05) , the expression of Wnt3a, LRP5, β-catenin in tibia [ (0.29±0.06) vs (0.78±0.13) , (0.30±0.05) vs (0.73±0.14) , (0.38±0.06) vs (1.01±0.18) , P<0.05], the content of ALP, OC and OPG in serum of model group were significantly lower than those of control group[ (40.27±7.52) vs (59.29±9.19) ng/ml, (252.45±42.95) vs (341.28±52.39) pg/ml, (0.40±0.06) vs (0.78±0.09) ng/ml, P<0.05) , and the contents of RANKL, TrACP and CTX-1 in serum were significantly higher than those of control group [ (17.79±2.84) vs (12.46±2.09) pg/ml, (56.45±7.79) vs (41.38±8.19) μmol/l, (19.26±3.14) vs (11.39±2.25) pg/ml, P<0.05]; the tibial bone mineral density, the content of calcium and phosphorus, the expression of Wnt3a, LRP5, β-catenin in tibia, the content of ALP, OC and OPG in serum of liraglutide group were significantly higher than those of control group, and the contents of RANKL, TrACP and CTX-1 in serum were significantly lower than those of control group. Conclusion Liraglutide can improve bone mineral density and bone metabolism in type 2 diabetic rats with osteoporosis, which may be related to activation of Wnt pathway. Key words: Liraglutide; Type 2 diabetes mellitus; Osteoporosis; Bone metabolism; Wnt pathway