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Background: Relationship between periodontitis (PD) and type 1 diabetes (T1D) has been reported, but the detailed pathogenesis requires further elucidation. This study aimed to reveal the genetic linkage between PD and T1D through bioinformatics analysis, thereby providing novel insights into scientific research and clinical treatment of the two diseases.Methods: PD-related datasets (GSE10334, GSE16134, GSE23586) and T1D-related datasets(GSE162689)were downloaded from NCBI Gene Expression Omnibus (GEO). Following batch correction and merging of PD-related datasets as one cohort, differential expression analysis was performed (adjusted p-value 2 fold change| > 0.5), and common differentially expressed genes (DEGs) between PD and T1D were extracted. Functional enrichment analysis was conducted via Metascape website. The protein-protein interaction (PPI) network of common DEGs was generated in The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Hub genes were selected by Cytoscape software and validated by receiver operating characteristic (ROC) curve analysis.Results: 59 common DEGs of PD and T1D were identified. Among these DEGs, 23 genes were commonly upregulated, and 36 genes were commonly downregulated in both PD- and T1D-related cohorts. Functional enrichment analysis indicated that common DEGs were mainly enriched in tube morphogenesis, supramolecular fiber organization, 9 + 0 non-motile cilium, plasma membrane bounded cell projection assembly, glomerulus development, enzyme-linked receptor protein signaling pathway, endochondral bone morphogenesis, positive regulation of kinase activity, cell projection membrane and regulation of lipid metabolic process. After PPI construction and modules selection, 6 hub genes (CD34, EGR1, BBS7, FMOD, IGF2, TXN) were screened out and expected to be critical in linking PD and T1D. ROC analysis showed that the AUC values of hub genes were all greater than 70% in PD-related cohort and greater than 60% in T1D-related datasets.Conclusion: Shared molecular mechanisms between PD and T1D were revealed in this study, and 6 hub genes were identified as potential targets in treating PD and T1D.

Bone-tissue defects affect millions of people worldwide. Despite being common treatment approaches, autologous and allogeneic bone grafting have not achieved the ideal therapeutic effect. This has prompted researchers to explore novel bone-regeneration methods. In recent decades, the development of bone tissue engineering (BTE) scaffolds has been leading the forefront of this field. As researchers have provided deep insights into bone physiology and the bone-healing mechanism, various biomimicking and bioinspired BTE scaffolds have been reported. Now it is necessary to review the progress of natural bone physiology and bone healing mechanism, which will provide more valuable enlightenments for researchers in this field. This work details the physiological microenvironment of the natural bone tissue, bone-healing process, and various biomolecules involved therein. Next, according to the bone physiological microenvironment and the delivery of bioactive factors based on the bone-healing mechanism, it elaborates the biomimetic design of a scaffold, highlighting the designing of BTE scaffolds according to bone biology and providing the rationale for designing next-generation BTE scaffolds that conform to natural bone healing and regeneration., Graphical abstract Bone-tissue engineering has become a promising treatment strategy for large bone defects. This work first introduces the advanced knowledge of bone biology, including the physiological microenvironment and healing process. Based on this concept, it further details the current biomimetic and bioactive bone-tissue engineering scaffolds promoting the healing process. Finally, it provides the future perspective in this field.Image 1, Highlights • Elaborate the advanced knowledge of bone physiological microenvironment and healing process. • Summary the biomolecules involved in the natural bone healing process which could be applied to BTE materials and scaffolds. • Detail the current biomimetic and bioinspired scaffolds based on the bone physiological microenvironment. • Review the delivery of bioactive factors based on the bone healing mechanism. • Discuss the current limitations that still need to be solved, and the feasible improvement and outlooks are proposed.

Objective. Based on RNA-sequencing (RNA-seq), the regulation of miRNAs differentially expressed in dental, periodontal, and alveolar bone tissue of orthodontic tree shrews on osteoblast skeleton under tension was investigated. Methods. Tree shrews were used to construct orthodontic models. We used RNA-seq to identify differentially expressed miRNAs in periodontal tissues of the treatment group and control group tree shrews. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for enrichment analysis. Human osteoblast MG63 was treated with 5000 U mechanical tension. Real-time quantitative polymerase chain reaction (RT-qPCR) detected the expression of miR-149 and ARFGAP with SH3 domain, Ankyrin repeat, and Ph domain 3 (ASAP3) mRNA. Western blot detected the protein levels of ASAP3, F-actin, osteogenic markers bone morphogenetic protein 2 (BMP2), and runt-related transcription factor 2 (RUNX2). Rhodamine phalloidin was used to observe the fluorescence intensity of F-actin. Validation of the targeting relationship between miR-149 and ASAP3 by dual luciferase reporter gene assay. Results. By performing miRNA-seq analysis on the dental and periodontal tissue of tree shrews in the treatment group and control group, we identified 51 upregulated miRNAs and 13 downregulated miRNAs. The expression of miR-149 in the dental and periodontal tissue of tree shrew and MG63 cells treated with mechanical tension was decreased, and miR-149 targeted ASAP3. Knockdown of ASAP3 inhibited the fluorescence intensity of F-actin in MG63 cells treated with 5000 U tension for 36 h, and overexpression of ASAP3 promoted the expression of F-actin and osteogenic markers BMP2 and RUNX2. Conclusions. These findings revealed that miR-149 could modulate osteoblast differentiation under orthodontics mechanical tension through targeting ASAP3.

Background. A growing number of studies have shown that long noncoding RNAs play an important role in osteoclast differentiation. However, there are few studies on the roles of lncRNA small nucleolar RNA host gene 15 (SNHG15) in osteoclast differentiation. Methods. The expressions of SNHG15, miR-381-3p, and never in mitosis-related kinase 2 (NEK2) mRNA were detected by real-time quantitative polymerase chain reaction (RT-qPCR); Western blot detected NEK2 and osteoclast markers (Cathepsin K, CTSK), matrix metalloproteinase 9 (MMP9), nuclear factor of activated T cell 2 (NFAT2), and tartrate-resistant acid phosphatase (TRAP) protein levels; cell proliferation was detected by Cell Counting Kit-8 (CCK-8), and the formation of osteoclasts was observed by TRAP staining; the F-actin skeleton was stained with tetramethylrhodamine isothiocyanate (TRITC) phalloidin; cell migration rate was detected by Transwell; dual-luciferase reporter gene assay and RNA-binding protein immunoprecipitation (RIP) assay verified the targeting relationship between miR-381-3p, SNHG15, and NEK2. Results. The expression of SNHG15 was increased in THP-1 cells stimulated by macrophage colony-stimulating factor (M-CSF)/receptor activator of nuclear factor-kappa B ligand (RANKL). Overexpression of SNHG15 significantly promoted the proliferation, migration, osteoclast differentiation, and expression of osteoclast markers CTSK, MMP9, NFAT2, and TRAP of THP-1 cells induced by M-CSF/RANKL. Knockdown of SNHG15 reversed this effect. Overexpression of SNHG15 downregulated the inhibitory effect of overexpression of miR-381-3p on the proliferation, migration, and differentiation of THP-1 cells induced by M-CSF/RANKL. Knockdown of miR-381-3p reversed the inhibitory effect of knockdown of NEK2 on the proliferation, migration, and differentiation of THP-1 cells induced by M-CSF/RANKL. Conclusion. SNHG15 acted as a ceRNA promoted the proliferation, migration, and differentiation of THP-1 cells induced by M-CSF/RANKL through sponging miR-381-3p to promote the expression of NEK2.

Objectives To systematically evaluate the effect of the surgery-first approach (SFA) on oral health-related quality of life (OHRQoL) in patients with dentofacial deformities. Materials and Methods An electronic database search and hand search of selected journals and references were carried out. Studies investigating the OHRQoL of patients receiving SFA with or without a control group were included. The risk of bias was assessed by the Cochrane risk of bias tool in randomized clinical trials (RCTs) and the Newcastle-Ottawa Scale in non-RCTs. Results A total of seven articles met the eligible criteria and were included, of which six were cohort studies and one was an RCT, and six assessed the OHRQoL of the SFA with conventional orthodontic–surgical treatment (COST) as a control and one without. A total of 214 patients were examined, with sample sizes in studies ranging from 9 to 50. A total of 3 articles successfully measured the OHRQoL both before and after treatment in both the SFA and conventional orthodontic–surgical treatment groups. A total of six cohort studies were classified as low to moderate risk of bias, and the RCT was classified as high. Conclusions The SFA could improve the OHRQoL of patients with dentofacial deformities similar to conventional orthodontic–surgical treatment at the end of complete treatment. In addition, it increases OHRQoL immediately at the beginning of treatment without a deterioration.

Biomimetic modification of hydroxyapatite on a polymer surface is a potent strategy for activating biological functions in bone tissue engineering applications. However, the polymer surface is bioinert, and it is difficult to introduce a uniform calcium phosphate (CaP) layer. To overcome this limitation, we constructed a specific nano-topographical structure onto a poly(e-caprolactone) substrate via surface-directed epitaxial crystallization. Formation of the CaP layer on the nano-topological surface was enhanced by 2.34-fold compared to that on a smooth surface. This effect was attributed to the abundant crystallization sites for CaP deposition because of the increased surface area and roughness. Bone marrow mesenchymal stromal cells (BMSCs) were used to examine the biological effect of biomineralized surfaces. We clearly demonstrated that BMSCs responded to surface biomineralization. Osteogenic differentiation and proliferation of BMSCs were significantly promoted on the biomineralized nano-topological surface. The expression of alkaline phosphatase and osteogenic-related genes as well as extracellular matrix mineralization was significantly enhanced. The proposed strategy shows potential for designing bone repair scaffolds.

The emergent need for new treatment methods for multi-drug resistant pathogens such as methicillin-resistant

Genome-wide association studies have identified a large number of susceptibility loci for exploring the genetic factors in the pathogenesis of type 2 diabetes (T2D). However, the specific mechanism by which these SNPs (especially in non-coding region) are involved in T2D pathogenesis still remains unclear. Recently, genetic variation is considered to affect the N(6)-methyladenosine (m6A) RNA modification, which is the most prevalent posttranscriptional messenger RNA modification. In this study, we identified a large number of T2D-associated m6A-SNPs from published T2D GWAS summary statistics and explored their potential mechanisms involved in T2D pathogenesis with public databases. In summary, among the 15,124 T2D-associated m6A-SNPs, 71 m6A-SNPs reached the genome-wide suggestive threshold (5.0E-05), while 51 of them showed eQTL signals. The leading SNP rs4993986 (C/G) is located next to the m6A modification site at the 3’ end of the HLA-DQB1 transcript, which is predicted to affect its m6A modification and regulate the expression of the HLA-DQB1 to participate in T2D pathogenesis. This m6A-SNP / gene expression / T2D triplets provides a new annotation for the pathogenic mechanism of T2D susceptibility loci identified by GWAS. Funding Statement: This study is supported by the National Natural Science Foundation of China (document no. 81801018). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Data was publicly available.

Circular RNAs (circRNAs) were initially regarded as by-products of aberrant splicing. But now, there are substantial evidence on their various roles in the regulation of genes during the development of organs and diseases. Consistent with these breakthroughs, it is experiencing rapid growth that circRNAs function as the important checkpoints during the osteogenesis. Therefore, characterizing the roles of circRNAs is useful and critical to better understanding the process of osteogenic differentiation, which could provide new avenues for the diagnosis and treatment of bone diseases, such as bone defects and osteoporosis. In this review, we presented a map of the interaction between circRNAs and the molecules of signaling pathways associated with osteogenesis, summarized the current knowledge of the biological functions of circRNAs during the osteogenic differentiation, figured out the limits of existing research works, and provided a novel look on the diagnostic and therapeutic methods of bone diseases based on circRNAs.

Bone defects caused heavy social and economic burdens worldwide. Nel‐like molecule, type 1 (NELL‐1) could enhance the osteogenesis and the repairment of bone defects, while the specific mechanism remains to be elucidated. Circular RNAs (circRNAs) have been found to play critical roles in the tissue development and serve as biomarkers for various diseases. However, it remains unclear that the expression patterns of circRNAs and the roles of them played in recombinant NELL‐1‐induced osteogenesis of human adipose‐derived stem cells (hASCs). In this study, we performed RNA‐sequencing to investigate the expression profiles of circRNAs in recombinant NELL‐1‐induced osteogenic differentiation and identified two key circRNAs, namely circRFWD2 and circINO80. These two circRNAs were confirmed to be up‐regulated during recombinant NELL‐1‐induced osteogenesis, and knockdown of them affected the positive effect of NELL‐1 on osteogenesis. CircRFWD2 and circINO80 could interact with hsa‐miR‐6817‐5p, which could inhibit the osteogenesis. Silencing hsa‐miR‐6817‐5p could partially reverse the negative effect of si‐circRFWD2 and si‐circINO80 on the osteogenesis. Therefore, circRFWD2 and circINO80 could regulate the expression of hsa‐miR‐6817‐5p and influence the recombinant NELL‐1‐induced osteogenic differentiation of hASCs. It opens a new window to better understanding the effects of NELL‐1 on the osteogenic differentiation of hASCs and provides potential molecular targets and novel methods for bone regeneration efficiently and safely.