Extracellular vesicles secreted by human gingival mesenchymal stem cells promote bone regeneration in rat femoral bone defects.

Extracellular vesicles (EVs), important components of paracrine secretion, are involved in various pathological and physiological processes of the body. In this study, we researched the benefits of EVs secreted by human gingival mesenchymal stem cells (hGMSC-derived EVs) in promoting bone regeneration, thereby providing new ideas for EVs-based bone regeneration therapy. Here, we successfully demonstrated that hGMSC-derived EVs could enhance the osteogenic ability of rat bone marrow mesenchymal stem cells and the angiogenic capability of human umbilical vein endothelial cells. Then, femoral defect rat models were created and treated with phosphate-buffered saline, nanohydroxyapatite/collagen (nHAC), a grouping of nHAC/hGMSCs, and a grouping of nHAC/EVs. The results of our study indicated that the combination of hGMSC-derived EVs and nHAC materials could significantly promote new bone formation and neovascularization with a similar effect to that of the nHAC/hGMSCs group. Our outcomes provide new messages on the role of hGMSC-derived EVs in tissue engineering, which exhibit great potential in bone regeneration treatment.

Local transplantation of GMSC-derived exosomes to promote vascularized diabetic wound healing by regulating the Wnt/ß-catenin pathways.

With the increasing number of diabetic patients, chronic wound healing remains a great challenge in clinical medicine. As one of the main components secreted by stem cells, the exosome is considered to be a promising candidate for promoting chronic wound healing. Here, gingival mesenchymal stem cell (GMSC)-derived exosomes (GMSC-Exo) were isolated and demonstrated to promote the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) by regulating the Wnt/ß-catenin signaling pathway in a diabetic-mimicking high glucose environment. In order to deliver GMSCs-Exo to the target site and prolong their local retention, porous microspheres consisting of poly-lactic-co-glycolic acid (PLGA), amphiphilic block copolymer (PLLA-PEG-PLLA), nano-hydroxyapatite (nHAP), and poly-ε-l-lysine (EPL) coating were fabricated through a double emulsion method and following surface treatment, hereafter referred to as PHE microspheres. PHE microspheres loaded with GMSCs-Exo were implanted into the full-thickness skin wound of a diabetic mouse model, resulting in significant vascularized wound healing when compared to a control group only injected with GMSCs-Exo suspension or filled with PHE microspheres. These findings indicated that the GMSCs-Exo-loaded porous microspheres could efficiently treat diabetic wounds and have promising potential for future clinical translations.

Extracellular vesicles: A potential future strategy for dental and maxillofacial tissue repair and regeneration.

Extracellular vesicles (EVs), nano-sized bilayer membrane structures containing lipids, proteins and nucleic acids, play key roles in intercellular communication. Compared to stem cells, EVs have lower tumorigenicity and immunogenicity, are easier to manage and cause fewer ethic problems. In recent years, EVs have emerged as a potential solution for tissue regeneration in stomatology through cell-free therapies. The present review focuses on the role of EVs in dental and maxillofacial tissue repair and regeneration, including in dental and periodontal tissue, maxilla and mandible bone, temporomandibular joint cartilage, peripheral nerve and soft tissue. We also make a brief overview on the mechanism of EVs performing functions. However, limitations and challenges in clinical application of EVs still exist and should be addressed in future researches.

Longitudinal investigation of idiopathic osteosclerosis lesions of the jaws in a group of Chinese orthodontically-treated patients using digital panoramic radiography.

BACKGROUND/PURPOSE: Idiopathic osteosclerosis (IO) is an intraosseous lesion of asymptomatic, non-expansive, radiopaque. The study aimed to investigate the prevalence and morphometric parameters of IO in orthodontic patients and variations in longitudinal observations and to assess the relationship between IO and orthodontic treatment. MATERIALS AND METHODS: Five hundred and seventy-one orthodontically-treated patients were reviewed. A cross-sectional study was performed with the evaluated parameters, including the age and sex of patients, as well as the number, shape, location and morphometric data of IO observed in panoramic radiography. Long-term behaviour of IO and orthodontic tooth movement were also observed. Also, a control group was set up for comparisons. RESULTS: Sixty-eight (11.3%) patients had 78 lesions all in the mandible with premolar/molar preference and no sex predilection. Lesions were located more commonly at apical and separate sites related to teeth. A large majority of lesions enlarged in the 10-19 years old group, while most lesions had no change in the 30-39 years old group. Hindrances of tooth movement and external root resorption around IO were not found in affected patients. CONCLUSION: IO is labile lesion that may develop in early stages of life, with little change occurring once the affected individual is mature and being relatively stable in the middle stage of life. Our study supports the hypothesis that IO may be developmental anatomic variations of normal bone. However, no obvious association between IO and orthodontic treatment was found in patients, which may be due to the limitations of two-dimensional shooting of panoramic radiography and the sample size.

Identification of hub lncRNA ceRNAs in multiple sclerosis based on ceRNA mechanisms.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, and the pathogenesis is influenced by genetic susceptibility. Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) play essential roles in complex diseases, including acting as competing endogenous RNAs (ceRNAs). However, the functional roles and regulatory mechanisms of lncRNAs acting as ceRNAs in MS are still unclear. In this study, we identified hub lncRNA ceRNAs in MS based on ceRNA mechanisms and annotated their functions. The lncRNA-associated ceRNA network (LACN) was constructed by integrating the expression profiles of lncRNA/mRNA and miRNA in MS and normal samples, and the experimentally validated interactions of lncRNA-miRNA and mRNA-miRNA. We found three hub lncRNA ceRNAs (XIST, OIP5-AS1, and CTB-89H12.4) using the network analysis and obtained 96 lncRNA-mediated competing triplets (LCTs, lncRNA-miRNA-mRNA) with the hub lncRNA ceRNAs, which constituted 3 hub ceRNA modules. The functional analysis identified 12 pathways enriched by the 3 hub lncRNA ceRNAs, of which 6 were confirmed to be related to MS. For example, XIST was enriched in the 'spliceosome' and 'RNA transport' related to the typing of MS, and CTB-89H12.4 was enriched in the 'mTOR signaling pathway,' a potential therapeutic target for MS. We dissected the expression patterns of the 96 LCTs in MS individually. LCT XIST-miR-326-HNRNPA1, for which the expression pattern in MS revealed that XIST and HNRNPA1 were up-regulated and miR-326 was down-regulated, consisted of risk RNAs for MS that were validated by other research. Therefore, XIST-miR-326-HNRNPA1 might play a central role in the pathogenesis of MS. These results will contribute to the discovery of novel biomarkers and the development of new therapeutic methods for MS.

A Novel RNA-Seq-Based Model for Preoperative Prediction of Lymph Node Metastasis in Oral Squamous Cell Carcinoma.

OBJECTIVE: To develop and validate a novel RNA-seq-based nomogram for preoperative prediction of lymph node metastasis (LNM) for patients with oral squamous cell carcinoma (OSCC). METHODS: RNA-seq data for 276 OSCC patients (including 157 samples with LNM and 119 without LNM) were downloaded from TCGA database. Differential expression analysis was performed between LNM and non-LNM of OSCC. These samples were divided into a training set and a test set by a ratio of 9 : 1 while the relative proportion of the non-LNM and LNM groups was kept balanced within each dataset. Based on clinical features and seven candidate RNAs, we established a prediction model of LNM for OSCC using logistic regression analysis. Tenfold crossvalidation was utilized to examine the accuracy of the nomogram. Decision curve analysis was performed to evaluate the clinical utility of the nomogram. RESULTS: A total of 139 differentially expressed RNAs were identified between LNM and non-LNM of OSCC. Seven candidate RNAs were screened based on FPKM values, including NEURL1, AL162581.1 (miscRNA), AP002336.2 (lncRNA), CCBE1, CORO6, RDH12, and AC129492.6 (pseudogene). Logistic regression analysis revealed that the clinical N stage (p < 0.001) was an important factor to predict LNM. Moreover, three RNAs including RDH12 (p value < 0.05), CCBE1 (p value < 0.01), and AL162581.1 (p value < 0.05) could be predictive biomarkers for LNM in OSCC patients. The average accuracy rate of the model was 0.7661, indicating a good performance of the model. CONCLUSION: Our findings constructed an RNA-seq-based nomogram combined with clinicopathology, which could potentially provide clinicians with a useful tool for preoperative prediction of LNM and be tailored for individualized therapy in patients with OSCC.

Genome-wide haplotype association study identify TNFRSF1A, CASP7, LRP1B, CDH1 and TG genes associated with Alzheimer's disease in Caribbean Hispanic individuals.

Alzheimer's disease (AD) is an acquired disorder of cognitive and behavioral impairment. It is considered to be caused by variety of factors, such as age, environment and genetic factors. In order to identify the genetic affect factors of AD, we carried out a bioinformatic approach which combined genome-wide haplotype-based association study with gene prioritization. The raw SNP genotypes data was downloaded from GEO database (GSE33528). It contains 615 AD patients and 560 controls of Caribbean Hispanic individuals. Firstly, we identified the linkage disequilibrium (LD) haplotype blocks and performed genome-wide haplotype association study to screen significant haplotypes that were associated with AD. Then we mapped these significant haplotypes to genes and obtained candidate genes set for AD. At last, we prioritized AD candidate genes based on their similarity with 36 known AD genes, so as to identify AD related genes. The results showed that 141 haplotypes on 134 LD blocks were significantly associated with AD (P<1E-4), and these significant haplotypes were mapped to 132 AD candidate genes. After prioritizing these candidate genes, we found seven AD related genes: APOE, APOC1, TNFRSF1A, LRP1B, CDH1, TG and CASP7. Among these genes, APOE and APOC1 are known AD risk genes. For the other five genes TNFRSF1A, CDH1, CASP7, LRP1B and TG, this is the first genetic association study which showed the significant association between these five genes and AD susceptibility in Caribbean Hispanic individuals. We believe that our findings can provide a new perspective to understand the genetic affect factors of AD.