Annexin A2 Improves the Osteogenic Differentiation of Mesenchymal Stem Cells Exposed to High-Glucose Conditions Through Lessening the Senescence

Osteoporosis is frequently found in chronic diabetic patients, and it results in an increased risk of bone fractures occurring. The underlying mechanism of osteoporosis in diabetic patients is still largely unknown. Annexin A2 (ANXA2), a family of calcium-binding proteins, has been reported to be involved in many biological process including bone remodeling. This study aimed to investigate the role of ANXA2 in mesenchymal stem cells (MSCs) during in vitro osteoinduction under high-glucose concentrations. Osteogenic gene expression, calcium deposition, and cellular senescence were determined. The high-glucose conditions reduced the osteogenic differentiation potential of the MSCs along with the lower expression of ANXA2. Moreover, the high-glucose conditions increased the cellular senescence of the MSCs as determined by senescence-associated β-galactosidase staining and the expression of p16, p21, and p53 genes. The addition of recombinant ANXA2 could recover the glucose-induced deterioration of the osteogenic differentiation of the MSCs and ameliorate the glucose-induced cellular senescence of the MSCs. A Western blot analysis revealed an increase in p53 and phosphorylated p53 (Ser 15), which was decreased by recombinant ANXA2 in MSC osteoblastic differentiation under high-glucose conditions. Our study suggested that the alteration of ANXA2 in high-glucose conditions may be one of the plausible factors in the deterioration of bones in diabetic patients by triggering cellular senescence.