Abstract

BackgroundPeriodontal 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 related to alveolar bone destruction in diabetic patients. SUMO modification has been reported in various diseases and is associated with an increasing number of biological processes, but previous studies have not focused on diabetic periodontitis. This study aimed to explore the role of IGF-1R in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in high glucose and control the multiple downstream damage signal factors.MethodsPDLSCs were isolated and cultured after extraction of impacted teeth from healthy donors or subtractive orthodontic extraction in adolescents. PDLSCs were cultured in the osteogenic medium with different glucose concentrations prepared by medical 5% sterile glucose solution. The effects of different glucose concentrations on the osteogenic differentiation ability of PDLSCs were studied at the genetic and cellular levels by staining assay, Western Blot, RT-PCR, Co-IP and cytofluorescence.ResultsWe found that SNAI2, RUNX2 expression decreased in PDLSCs cultured in high glucose osteogenic medium compared with that in normal glucose osteogenic medium, which were osteogenesis-related marker. In addition, the IGF-1R expression, sumoylation of IGF-1R and osteogenic differentiation in PDLSCs cultured in high glucose osteogenic medium were not consistent with those cultured in normal glucose osteogenic medium. However, osteogenic differentiation of PDLCSs enhanced after adding IGF-1R inhibitors to high glucose osteogenic medium.ConclusionOur data demonstrated that SUMO1 modification of IGF-1R inhibited osteogenic differentiation of PDLSCs by binding to SNAI2 in high glucose environment, a key factor leading to alveolar bone loss in diabetic patients. Thus we could maximize the control of multiple downstream damage signaling factors and bring new hope for alveolar bone regeneration in diabetic patients.

Highlights

  • Diabetes mellitus (DM) is one of the most prevalent chronic diseases worldwide, and the prevalence of DM in adults is about 10% [1]

  • The results showed that 21 days later, compared with 5.5 mmol/L osteogenic medium, the amount of mineralized nodule formation of periodontal ligament stem cells (PDLSCs) gradually decreased by means of concentration dependent, and the osteogenic differentiation ability of PDLSCs decreased (Fig. 1a) as glucose concentration increased

  • The results showed that the level of RUNX2 in PDLSCs at 14 days of osteogenic induction gradually decreased in a glucose concentrationdependent manner

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Summary

Introduction

Diabetes mellitus (DM) is one of the most prevalent chronic diseases worldwide, and the prevalence of DM in adults is about 10% [1]. We often find that diabetic patients have gum recession and crown elongation, while X-rays can show horizontal resorption of the alveolar bone between the teeth. There are segments of common clinical treatment, such as supragingival scaling, subgingival scraping, local rinsing, loose tooth fixation, etc., which are extremely limited All of these tell us that diabetes is a very important factor in the loss of alveolar bone. The insulin-like growth factor 1 receptor (IGF-1R) plays an important role in regulating functional impairment associated with diabetes. It is unclear whether IGF-1R expression in periodontal tissue is related to alveolar bone destruction in diabetic patients. This study aimed to explore the role of IGF-1R in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in high glucose and control the multiple downstream damage signal factors

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