Rosuvastatin promotes osteogenic differentiation of mesenchymal stem cells in the rat model of osteoporosis by the Wnt/β-catenin signal

Abstract

Objective: The aim of this study was to explore the promoting effect of rosuvastatin on the osteogenic differentiation of mesenchymal stem cells in the rat model of osteoporosis through the Wnt/β-catenin signal.

Materials and methods: A total of 30 rats were purchased from the Animal Research Center of Shanxi Medical University. All rats were randomly allocated into three groups, including: group A (control group, n=10), group B (ovariectomized group, n=10), and group C (rosuvastatin gavage group, n=10). The bone metabolism indexes, bone mineral density (BMD) and the Wnt/β-catenin signaling pathway-related proteins in blood samples of rats in each group were measured, respectively. Furthermore, the bone marrow mesenchymal stem cells of rats were used for alkaline phosphatase (ALP) staining. All data were analyzed using the Statistical Product and Service Solutions (SPSS) 22.0 software (IBM Corp., Armonk, NY, USA).

Results: The rats firstly received 9 consecutive weeks of feeding with drug intervention. The imaging results revealed that trabecular thickness in group A was significantly higher than that of group B and group C, showing statistically significant differences (p<0.05). After 9 consecutive weeks of feeding with drug intervention, BMD of the femurs of rats in group A and group C was significantly higher than that of group B, showing statistically significant differences (p<0.05). However, there was no significant difference in BMD between group A and group C (p>0.05). The level of calcium representing bone absorption level in serum of rats in group B was remarkably higher than that of group A, and the difference was statistically significant (p<0.05). However, the level of ALP representing bone absorption level in the serum of rats in group B was significantly lower than that of group A (p<0.05). No significant differences were found in the levels of calcium and ALP that represented bone absorption level between group C and group A (p>0.05). Meanwhile. the levels of phosphorus in the three groups were similar, showing no statistically significant difference (p>0.05). Moreover, the expression of ALP-positive cells in the rats of group A and group C was markedly higher than that of group B (p<0.05). After drug intervention through feeding for 9 consecutive weeks, no evident difference was found in the relative expression of Wnt/β-catenin signaling pathway-related protein glycogen synthase kinase-3β (GSK-3β) among the three groups. The relative expression of the protein phosphorylated GSK-3β (p-GSK-3β) in group C was significantly lower than that of group B (p<0.05). Furthermore, the relative protein expressions of β-catenin and cyclin D1 in group C were significantly higher than those in group B (p<0.05).

Conclusions: Rosuvastatin can improve bone metabolism in osteoporosis rats and increasing BMD of bone tissues in rats with osteoporosis. Besides, the Wnt/β-catenin signaling pathway plays a crucial role in the regulation of the stem cell self-renewal and bone genesis.