Inhibition of the negative effect of high glucose on osteogenic differentiation of bone marrow stromal cells by silicon ions from calcium silicate bioceramics

Human bone marrow stem cells (hBMSCs) are exploited for miscellaneous applications in bone tissue engineering where they are mainly used as seed cells. However, high glucose (HG) environment has negative impacts on the proliferation and osteogenic differentiation of hBMSCs, thus reducing the bone formation in diabetic patients. In our former research works, we discovered that silicon (Si) ions extracted from silicate-based bioceramics are able to stimulate the proliferation and osteogenic differentiation of hBMSCs under normal culture condition. This study aimed to investigate if Si ions could prevent HG-induced inhibition of proliferation and osteogenesis of hBMSCs. We found that 2.59 ppm concentration of Si ions promoted the proliferation of hBMSCs under HG condition. The results from alkaline phosphatase (ALP) activity assay, Alizarin red S staining and quantitative real-time PCR analysis of osteogenic genes (BMP2, RUNX2, ALP, COL1 and OCN) demonstrated that the 15.92 ppm concentration of Si ions prevented HG-induced inhibition of the osteogenic differentiation of hBMSCs. Moreover, application of Si ions reduced the level of reactive oxygen species in HG-treated hBMSCs. In HG-treated hBMSCs following 15.92 ppm Si ions treatment, activation of BMP2/SMAD signaling pathway was detected, as indicated by the increased expression of BMP2 receptors and its downstream genes such as SMAD1, SMAD4 and SMAD5. Taken together, we provide evidence that the specific concentration of Si ions compensated HG-induced inhibition of proliferation and osteogenic differentiation of hBMSCs through antioxidant effect and modulation of BMP2/SMAD pathway. The results suggest that silicate-based bioceramics might be good scaffold biomaterials for bone engineering applications in diabetes patients.