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.

Discordant abundances of different immune cell subtypes is regarded to be an essential feature of tumour tissue. Direct studies in Prostate cancer (PC) of intratumoral immune heterogeneity characterized by immune cell subtype, are still lacking. Using the single sample gene set enrichment analysis (ssGSEA) algorithm, the abundance of 28 immune cells infiltration (ICI) were determined for PC. A NMF was performed to determine tumour-sample clustering based on the abundance of ICI and PFS information. Hub genes of clusters were identified via weighted gene co-expression network analysis (WGCNA). The multivariate dimensionality reduction analysis of hub genes expression matrix was carried out via principal component analysis (PCA) to obtain immune score (IS). We analysed the correlation between clustering, IS and clinical phenotype. We divided the 495 patients into clusterA (n = 193) and clusterB (n = 302) on the basis of ICI and PFS via NMF. The progression-free survival (PFS) were better for clusterA than for clusterB (p < 0.001). Each immune cell subtypes was more abundant in clusterA than in clusterB (p < 0.001). The expression levels of CTAL-4 and PD-L1 were lower in clusterB than in clusterA (p < 0.001 and p = 0.006). We obtained 103 hub genes via WGCNA. In the training and validation cohorts, the prognosis of high IS group was worse than that of the low IS group (p < 0.05). IS had good predictive effect on 5-year PFS. The expression of immune checkpoint genes was higher in the low IS group than in the high IS group (p < 0.01). Patients with low IS and receiving hormone therapy had better prognosis than other groups. The combination of IS and clinical characteristics including lymph node metastasis and gleason score can better differentiate patient outcomes than using it alone. IS was a practical algorithm to predict the prognosis of patients. Advanced PC patients with low IS may be more sensitive to hormone therapy. CXCL10, CXCL5, MMP1, CXCL12, CXCL11, CXCL2, STAT1, IL-6 and TLR2 were hub genes, which may drive the homing of immune cells in tumours and promote immune cell differentiation.

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Background: The temporomandibular joint (TMJ) is a complex joint consisting of the mandibular condyle, temporal articular surface, and articular disc. The functions of mastication, swallowing and articulation are accomplished by the movements of the TMJ. To date, the TMJ has been studied more extensively, but the study of the TMJ is limited by the type of TMJ cells, their differentiation, and their interrelationship during growth and development is unclear. The aim of this study is to establish a molecular cellular developmental atlas of the human TMJ by single-cell RNA sequencing, which will contribute to understanding and solving. Results: We performed a comprehensive transcriptome analysis of TMJ tissue from 3- and 4-month-old human embryos using single-cell RNA sequencing. A total of 15,624 cells were captured and the gene expression profiles of 15 cell populations in human TMJ were determined, including 14 known cell types and a previously unknown cell type named "transition state cells (TSCs)". Immunofluorescence assays confirmed that TSCs are not the same cell cluster as mesenchymal stem cells (MSCs). Pseudotime trajectory and RNA velocity analysis showed that MSCs transformed into TSCs, and TSCs further differentiated into tenocytes, hypertrophic chondrocytes and osteoblasts. In addition, chondrocytes were detected only in 4-month-old human embryonic TMJ. Conclusions: Our study provides an atlas of the earlier cellular development of human embryonic TMJ tissue, which will contribute to a deeper understanding of the pathophysiology of TMJ tissue during repair and ultimately help to solve clinical problems.

TEAD4 is a member of the TEA domain (TEAD) family of transcription factors. It plays a key regulatory role in embryonic development, tissue homeostasis and cancer progression. Its expression is related to the regulation of a variety of inflammations. MicroRNA can regulate the expression of target genes and play an important role in various physiological and pathological processes. In view of the important role of TEAD4 and microRNA-629-5p (miR-629-5p) in inflammation, and based on the findings of bioinformatics research, we selected miR-629-5p as the focus of our study. In inflammatory dental pulp, we found that the expression of miR-629-5p was increased, while the expression of TEAD4 was decreased. We used Porphyromonas gingivalis lipopolysaccharide (LPS) as a stimulator of dental pulp stem cells (DPSCs) to simulate the inflammatory environment of dental pulp. The mineralization ability of LPS-stimulated DPSCs was significantly inhibited, while the level of miR-629-5p increased and the level of TEAD4 decreased. Inhibition of miR-629-5p can reverse the odontogenic defects of DPSCs treated with LPS. In addition, the expression of miR-629-5p in DPSCs was negatively correlated with the expression of TEAD4. In conclusion, miR-629-5p can inhibit the odontogenic differentiation of human dental pulp stem cells and the mechanism may be related to its role in downregulation of TEAD4 expression.