SUMO1 modification of IGF-1R combining with SNAI2 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 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. Methods PDLSCs 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. Results We 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. Conclusion Our 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.

Metformin combats high glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells via inhibition of the NPR3-mediated MAPK pathway

“…However, high glucose-induced damage to PDLSCs presents a major challenge to their applications in diabetic individuals [16]. Accumulating evidence indicates that PDLSCs incubated in high glucose exhibit impaired stem cell performance, including reduced proliferation and multilineage differentiation potentials, which would compromise the therapeutic effect of these cells [17,18]. Therefore, enhancing the stemness of PDLSCs under high glucose is important for periodontal tissue regeneration in diabetic individuals.…”

LncRNA JHDM1D‐AS1 promotes osteogenic differentiation of periodontal ligament cells by targeting miR‐532‐5p to activate IGF1R signaling

“…IGF1R glucose-induced osteogenic differentiation of PDLCs. 43 Through downstream targets, IGF1R regulates several signaling pathways, such as PI3K/AKT, 44 RAS/RAF/ERK 45 and STAT3 signaling pathways. 46 Intriguingly, it has been reported that the IGF1R/PI3K/AKT axis positively regulates Notch ligand-induced activation of Notch signaling.…”

ATBF1 is a potential diagnostic marker of histological grade and functions via WNT5A in breast cancer

“…Zhou et al [ 45 ] found that high glucose induced SUMOylation of Smad4 via SUMO2/3 and activated TGF-β/Smad signaling in mesangial cells. SUMOylation of IGF-1R in periodontal ligament stem cells cultured in high glucose medium inhibited osteogenic differentiation [ 46 ]. Lysine 2806 is an important site for ATBF1 SUMOylation, whose mutation prevents MDA-MB-231 cells from forming tumors in nude mice [ 21 ].…”