Yongchao Gou

Immunomodulatory properties of dental tissue‐derived mesenchymal stem cells

In addition to their well-established self-renewal and multipotent differentiation properties, mesenchymal stem cells (MSCs) also possess potent immunomodulatory functions both in vitro and in vivo, which render them a potential novel immunotherapeutic tool for a variety of autoimmune and inflammation-related diseases. The major mechanisms may involve (1) the secretion of an array of soluble factors such as prostaglandin E2 (PGE2 ), indoleamine 2, 3-dioxygenase (IDO), transforming growth factor-β (TGF-β), and human leukocyte antigen G5 (HLA-G5); (2) interactions between MSCs and immune cells such as T cells, B cells, macrophages, and dendritic cells. Recently, increasing evidence has supported that MSCs derived from dental tissues are promising alternative sources of multipotent MSCs. We here provide a thorough and extensive review about new findings in the immunomodulatory functions of MSCs derived from several dental tissues, including dental pulp, periodontal ligament, gingiva, exfoliated deciduous teeth, apical papilla, and dental follicle, respectively. The immunomodulatory properties of dental MSCs place them as a more accessible cell source than bone marrow-derived MSCs for cell-based therapy of immune and inflammation-related diseases.

The endothelial-mesenchymal transition (EndMT) and tissue regeneration.

Recent studies have brought endothelial-mesenchymal transition (EndMT) as a special perspective of epithelial- mesenchymal transition (EMT) into eyes. Traditionally, EndMT is considered as a source for fibroblasts and myofibroblasts, and it is extensively investigated in physiologic cardiac development as well as in pathologic tumor and fibrosis. Recently, new studies have found that EndMT-transformed cells had stemness, which means they could differentiate into chondroblasts, osteoblasts, and adipoblasts in differential culture, respectively. This gives EndMT a bright application future in tissue engineering and regeneration, especially for the formation of cartilage and bone.

Effects of Hypoxia on the Immunomodulatory Properties of Human Gingiva–Derived Mesenchymal Stem Cells

The environment of bone marrow mesenchymal stem cells (MSCs) is hypoxic, which plays an important role in maintaining their self-renewal potential and undifferentiated state. MSCs have been proven to possess immunomodulatory properties and have been used clinically to treat autoimmune diseases. Here, we tested the effects of hypoxia on the immunomodulatory properties of MSCs and examined its possible underlying mechanisms. We found that hypoxic stimulation promoted the immunomodulatory properties of human gingiva–derived mesenchymal stem cells (hGMSCs) by enhancing the suppressive effects of hGMSCs on peripheral blood mononuclear cells (PBMCs). The proliferation of PBMCs was significantly inhibited, while the apoptosis of PBMCs was increased, which was associated with the Fas ligand (FasL) expression of hGMSCs. The in vivo study showed that systemically infused hGMSCs could enhance skin wound repair, and 24-h hypoxic stimulation significantly promoted the reparative capacity of hGMSCs. For mechanism, hGMSC treatment inhibited the local inflammation of injured skin by suppressing the inflammatory cells, reducing the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), and increasing anti-inflammatory cytokine interleukin-10 (IL-10), which was promoted by hypoxia. Hypoxia preconditioning may be a good optimizing method to promote the potential of MSCs for the future cell-based therapy.

The Immune Factors Involved in the Pathogenesis, Diagnosis, and Treatment of Sjogren's Syndrome

Sjogrens syndrome (SS) is a systemic, autoimmune disorder characterized by salivary insufficiency and lymphocytic infiltration of the exocrine glands. Even though the mechanism of its pathology and progression has been researched ever since its discovery, the roles of different parts of immune system remain inconclusive. There is no straightforward and simple theory for the pathogenesis and diagnosis of Sjogrens syndrome because of the multiple kinds and functions of autoantibodies, changing proportion of different T-lymphocyte subsets with the progression of disease, unsuspected abilities of B lymphocytes discovered recently, crosstalk between cytokines connecting the factors mentioned previously, and genetic predisposition that contributes to the initiation of this disease. On the other hand, the number of significant reports and open-label studies of B-cell depletion therapy showing clinical efficacy in sjogrens syndrome has continued to accumulate, which provides a promising future for the patients. In a word, further elucidation of the role of different components of the immune system will open avenues for better diagnosis and treatment of SS, whose current management is still mainly supportive.

Osteoimmunology in orthodontic tooth movement

The skeletal and immune systems share a multitude of regulatory molecules, including cytokines, receptors, signaling molecules, and signaling transducers, thereby mutually influencing each other. In recent years, several novel insights have been attained that have enhanced our current understanding of the detailed mechanisms of osteoimmunology. In orthodontic tooth movement, immune responses mediated by periodontal tissue under mechanical force induce the generation of inflammatory responses with consequent alveolar bone resorption, and many regulators are involved in this process. In this review, we take a closer look at the cellular/molecular mechanisms and signaling involved in osteoimmunology and at relevant research progress in the context of the field of orthodontic tooth movement.

Transcription Factors in Craniofacial Development: From Receptor Signaling to Transcriptional and Epigenetic Regulation

Craniofacial morphogenesis is driven by spatial-temporal terrains of gene expression, which give rise to stereotypical pattern formation. Transcription factors are key cellular components that control these gene expressions. They are information hubs that integrate inputs from extracellular factors and environmental cues, direct epigenetic modifications, and define transcriptional status. These activities allow transcription factors to confer specificity and potency to transcription regulation during development.

Comparison of methods for localization of impacted maxillary canines by panoramic radiographs.

OBJECTIVESnThe objective of this study was to compare three methods for localization of impacted maxillary canines using only conventional panoramic radiographs.nnnMETHODSnThe panoramic radiographs of 94 patients (102 impacted maxillary canines) were reviewed and evaluated using the methods magnification, angulation and superimposition. The actual positions of them were decided with cone beam CT images. The predicted positions of impacted canines from the magnification and angulation methods were compared using the McNemar χ(2) test. Sensitivity, specificity, accuracy, positive-likelihood ratio and negative-likelihood ratio were calculated. The canine-incisor index values and α angles of palatally and bucally non-rotated impacted canines were compared using the Mann-Whitney U test.nnnRESULTSnThe statistical analysis revealed that there was a significant difference between the magnification and angulation methods (pu2009<u20090.01). Using the magnification method, 68.00% of buccal canines and 69.57% of palatal canines could be localized correctly. The results of the angulation method were 28.57% and 84.91%, respectively. The sensitivity of the angulation method for buccal canines was very low. In the superimposition method, 82.98% of the superimposing samples were palatal.nnnCONCLUSIONSnThe magnification and angulation methods were not reliable methods for locating the impacted canine with a single panoramic radiograph. Magnification was more successful than the angulation method. Further research is needed on the magnification method. The image superimposition method could be used as an adjunct to others.

Transcription Factors in Craniofacial Development

Craniofacial morphogenesis is driven by spatial-temporal terrains of gene expression, which give rise to stereotypical pattern formation. Transcription factors are key cellular components that control these gene expressions. They are information hubs that integrate inputs from extracellular factors and environmental cues, direct epigenetic modifications, and define transcriptional status. These activities allow transcription factors to confer specificity and potency to transcription regulation during development.

Smad6 Methylation Represses NFκB Activation and Periodontal Inflammation

The balance between pro- and anti-inflammatory signals maintains tissue homeostasis and defines the outcome of chronic inflammatory diseases such as periodontitis, a condition that afflicts the tooth-supporting tissues and exerts an impact on systemic health. The induction of tissue inflammation relies heavily on Toll-like receptor (TLR) signaling, which drives a proinflammatory pathway through recruiting myeloid differentiation primary response gene 88 (MyD88) and activating nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB). TLR-induced production of proinflammatory cytokines and chemokines is reined in by anti-inflammatory cytokines, including the transforming growth factor β (TGFβ) family of cytokines. Although Smad6 is a key mediator of TGFβ-induced anti-inflammatory signaling, the exact mechanism by which TGFβ regulates TLR proinflammatory signaling in the periodontal tissue has not been addressed to date. In this study, we demonstrate for the first time that the ability of TGFβ to inhibit TLR-NFκB signaling is mediated by protein arginine methyltransferase 1 (PRMT1)–induced Smad6 methylation. Upon methylation, Smad6 recruited MyD88 and promoted MyD88 degradation, thereby inhibiting NFκB activation. Most important, Smad6 is expressed and methylated in the gingival epithelium, and PRMT1-Smad6 signaling promotes tissue homeostasis by limiting inflammation. Consistent with this, disturbance of Smad6 methylation exacerbates inflammation and bone loss in experimental periodontitis. The dissected mechanism is therapeutically important, as it highlights the manipulation of PRMT1-Smad6 signaling as a novel promising strategy to modulate the host immune response in periodontitis.

Prmt1 regulates craniofacial bone formation upstream of Msx1

Protein arginine methylation has been recently identified as an important form of post-translational modification (PTM). It is carried out by the protein arginine methyltransferase (PRMT) family of enzymes, which in mammals consists of nine members. Among them, PRMT1 is the major arginine methyltransferase and participates in transcription, signal transduction, development and cancer. The function of PRMT1 in craniofacial development remains unclear. We generated Wnt1-Cre;Prmt1fl/fl mice with cranial neural crest (CNC)-specific deletion of Prmt1 and compared CNC-derived craniofacial bones from newborn control and Wnt1-Cre;Prmt1fl/fl mice. The size, surface area and volume of the premaxilla, maxilla, palatine bone, frontal bone, and mandible were analyzed using three-dimensional (3D) micro-computed tomography (microCT). We found that Prmt1 deficiency led to alterations in craniofacial bones including the premaxilla, maxilla, palatine bone, frontal bone, and mandible, as well as defects in the incisor and alveolar bone, recapitulating changes seen in Msx1-deficient mice. We further determined that Prmt1 depletion resulted in significant downregulation of Msx1 in calvaria-derived preosteoblast and primordium of frontal bone and mandible. Our study reveals critical roles of PRMT1 in the formation of CNC-derived craniofacial bones and suggests that Prmt1 is an upstream regulator of Msx1 in craniofacial bone development.