The effect of high glucose on the biological characteristics of nucleus pulposus-derived mesenchymal stem cells.

Abstract

Diabetes mellitus (DM) is a dependent risk factor in the progression of intervertebral disc degeneration (IVDD). High glucose supply has negative effects on nucleus pulpous (NP) cell and mesenchymal stem cell (MSC) biology. However, the effect of hyperglycaemia on the biological characterization of nucleus pulpous-derived mesenchymal stem cell (NPMSC) has not been investigated previously. Therefore, further exploration of the effects of DM-associated hyperglycaemia on NPMSC biology is important to better understand and develop endogenous repair strategies of DM patient-associated IVDD. Therefore, the cell biological characteristics were compared between NPMSC cultured in media with low glucose concentration (LG-NPMSC) and high glucose concentration (HG-NPMSC). The results demonstrated that HG-NPMSC showed significantly decreased cell proliferation, colony formation ability, migration and wound-healing capability compared with those of LG-NPMSC. HG-NPMSC also showed significantly decreased expressions of stemness genes and mRNA and protein expressions of silent information regulator protein 1 (SIRT1), SIRT6, hypoxia inducible factor-1α (HIF-1α) and glucose transporter 1 (GLUT-1), whereas increased cell apoptosis, cell senescence and caspase-3 expression. These results suggest that high glucose may decrease proliferation and stemness maintenance ability and increase apoptosis and senescence of NPMSC. SIGNIFICANCE OF THE STUDY: We found that high glucose concentration significantly decreased cell proliferation, colony formation ability, migration and wound-healing capability of nucleus pulposus-derived mesenchymal stem cells. Moreover, high glucose cultured nucleus pulposus-derived mesenchymal stem cells showed significantly decreased expression of stemness genes, related mRNA and protein, whereas increased cell apoptosis, cell senescence and expression of caspase-3. The present study indicated that better control of high concentration glucose in the early stage of diabetes mellitus should be recommended to prevent or limit intervertebral disc degeneration.