| Purpose: During the period of bone regeneration,bone marrow stromal cells(BMSCs)play an important role in bone restoration.However,the bone disorders related with type 2 diabetes mellitus lead to poor osteointegration of dental implant and delayed restoration of bone defect.So how the type 2 diabetic BMSCs have effect on bone regeneration gradually becomes a new focus.The purpose of the study was to evaluate the differences between type 2 diabetic rat BMSCs and normal rat BMSCs in cell proliferation,osteogenic differentiation and new bone formation.The changes of Wnt signaling pathway in type 2 diabetic rat BMSCs were also analyzed in the study.Moreover,the cell proliferation and osteogenic differentiation of BMP2 induced type 2 diabetic rat BMSCs were studied to evaluate the effect of BMP2 on type 2 diabetic BMSCs.The study would provide the theoretical basis for the treatment on bone disorders related to type 2 diabetes mellitus.Methods: 1.Type 2 diabetic rat model was incuded with high fat diet and low dose streptozotocin.The blood glucose level,body weight and blood insulin concentration were measured in the study.2.MTT assay,ALP activity,alizarin red staining,real-time PCR and new bone formation analyses were used to compare the osteogenic potential of type 2 diabetic and normal rat BMSCs.The changes of Wnt signaling pathway in two groups were detected.3.The influence of BMP2 on type 2 diabetic rat BMSCs was analyzed for cell proliferation,ALP activity,alizarin red staining,real-time PCR and new bone formation.In addition,XAV939 was used to evaluate the effect of BMP2 on Wnt signaling pathway.Results: 1.Type 2 diabetic rat model could be successfully established by high fat diet and low dose streptozotocin.The blood glucose level,body weight and blood insulin concentration were in accordance with type 2 diabetes mellitus.2.Type 2 dibetic rat BMSCs were impaired in cell proliferation,osteogenic differentiation and new bone formation compared with normal BMSCs.The impaired ability of diabetic BMSCs was related to the inhibition of Wnt signaling pathway.3.BMP2 could promot cell proliferation,osteogenic differentiation and new bone formation in type 2 diabetic rat BMSCs.The expression levels of Wnt signaling related genes and proteins were upragulated in type 2 diabetic BMSCs.Conclusion: 1.High fat diet and low dose streptozotocin induced type 2 diabetic rat model was stable and reliable.2.The abilities of cell proliferation,osteogenic differentiation and new bone formation in type 2 diabetic were impaired with the inhibition of Wnt signaling.3.BMP2 could improve the impaired osteogenic potential of type 2 diabetic BMSCs through stimulating Wnt signaling pathway. |
