SUMO1 modification of IGF-1R combining with SLUG inhibited osteogenic differentiation of PDLSCs stimulated by high glucose

Abstract

Background: Periodontal disease, an oral disease characterized by loss of alveolar bone and progressive teeth loss, is the sixth major complication of diabetes. It is spreading worldwide as it is difficult to be cured. The insulin-like growth factor 1 receptor (IGF-1R) plays an important role in regulating functional impairment associated with diabetes. However, it is unclear whether IGF-1R expression in periodontal tissue is associated with periodontal bone tissue destruction in diabetic patients. SUMO modification has been reported in various diseases and are associated with an increasing number of biological processes, but previous studies have not focused on diabetic periodontitis.Methods: Periodontal membrane stem cells (PDLSCs) were isolated and cultured from healthy human obstructed teeth after extraction or adolescent orthodontic subtractive extraction. PDLSCs were cultured with medical 5% sterile glucose solution formulated as osteogenic differentiation induction solution with different glucose concentrations. The effects of different glucose concentrations on the osteogenic differentiation ability of PDLSCs were investigated at the genetic and cellular levels using staining assay, Western Blot, RT-PCR, Co-IP and cytofluorescence.Results: We found that SLUG, RUNX2 expression was decreased in PDLSCs cultured in high glucose osteogenic induction solution compared with normal glucose osteogenic induction solution. In addition, the IGF-1R expression levels, osteogenic differentiation and sumoylation of IGF-1R in PDLSCs cultured in high glucose osteogenic induction solution were not consistent with those cultured in normal glucose osteogenic induction solution.Conclusion: Our data demonstrated that SUMO1 modification of IGF-1R in high glucose environment inhibited osteogenic differentiation of PDLSCs by binding to SLUG, a key factor leading to periodontal bone tissue loss in diabetic patients. Thus we can maximize the control of multiple downstream damage signaling factors and bring new hope for periodontal tissue regeneration in diabetic patients.