Cementum, a specialized bony layer covering an entire molar root surface, anchors teeth into alveolar bone. Gli1, a key transcriptional activator in Hedgehog signaling, has been identified as a mesenchymal progenitor cell marker in various tissues, including the periodontal ligament (PDL). To address the mechanisms by which Gli1+ progenitor cells contribute to cementogenesis, we used the Gli1lacZ/+ knock-in line to mark Gli1+ progenitors and the Gli1CreERT2/+; R26RtdTomato/+ line (named Gli1Lin) to trace Gli1 progeny cells during cementogenesis. Our data unexpectedly displayed a biphasic feature of Gli1+ PDL progenitor cells and cementum growth: a negative relationship between Gli1+ progenitor cell number and cementogenesis but a positive correlation between Gli1-derived acellular and cellular cementoblast cell number and cementum growth. DTA-ablation of Gli1Lin cells led to a cementum hypoplasia, including a significant reduction of both acellular and cellular cementoblast cells. Gain-of-function studies (by constitutive stabilization of β-catenin in Gli1Lin cells) revealed a cementum hyperplasia. A loss of function (by conditional deletion of β-catenin in Gli1+ cells) resulted in a reduction of postnatal cementum growth. Together, our studies support a vital role of Gli1+ progenitor cells in contribution to both types of cementum, in which canonical Wnt/β-catenin signaling positively regulates the differentiation of Gli1+ progenitors to cementoblasts during cementogenesis.

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.

Opaqueness of animal tissue can be attributed mostly to light absorption and light scattering. In most noncleared tissue samples, confocal images can be acquired at no more than a 100-µm depth. Tissue-clearing techniques have emerged in recent years in the neuroscience field. Many tissue-clearing methods have been developed, and they all follow similar working principles. During the tissueclearing process, chemical or physical treatments are applied to remove components blocking or scattering the light. Finally, samples are immersed in a designated clearing medium to achieve a uniform refractive index and to gain transparency. Once the transparency is reached, images can be acquired even at several millimeters of depth with high resolution. Tissue clearing has become an essential tool for neuroscientists to investigate the neural connectome or to analyze spatial information of various types of brain cells. Other than neural science research, tissue-clearing techniques also have applications for bone research. Several methods have been developed for clearing bones. Clearing treatment enables 3-dimensional imaging of bones without sectioning and provides important new insights that are difficult or impossible to acquire with conventional approaches. Application of tissue-clearing technique on dental research remains limited. This review will provide an overview of the recent literature related to the methods and application of various tissue-clearing methods. The following aspects will be covered: general principles for the tissue-clearing technique, current available methods for clearing bones and teeth, general principles of 3-dimensional imaging acquisition and data processing, applications of tissue clearing on studying biological processes within bones and teeth, and future directions for 3-dimensional imaging.

Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of malignant epithelial tumors of the oral and maxillofacial region. OSCC has high rate of metastasis and poor prognosis. Tobacco and/or alcohol consumption and human papillomavirus infection are relatively exact susceptibility factors for OSCC, but the specific process of oral mucosal carcinogenesis and progression is very complicated. microRNA-302b (miR-302b) could regulate various characteristics of many tumor cells, such as proliferation and apoptosis, but its role and mechanism in OSCC have not been reported. This research aims to study the effect of miR-302b on the invasion and migration ability of OSCC and the mechanism by which it functions as well as to identify new prognostic indicators and therapeutic targets for OSCC patients. Functional studies showed that the miR-302b level was negatively correlated with the invasion and migration ability of OSCC. The studies also showed that the overexpression of miR-302b could attenuate the invasion and migration ability of OSCC cells and reduce lymphangiogenesis and the lung metastasis rate of OSCC cells in a mouse model. Mechanistic studies were performed by quantitative polymerase chain reactions, luciferase assays, and RNA pull-down experiments. The results verified that frizzled class receptor 6 (FZD6) is a target gene of miR-302b in OSCC that could promote cell invasion and migration. Clinical studies demonstrate that the protein expression level of FZD6 was higher in OSCC and metastatic lymph nodes than in normal oral mucosa epithelium. Taken together, these data showed that miR-302b could inhibit the invasion and migration ability of OSCC cells by targeting and downregulating FZD6, thereby inhibiting OSCC metastasis. As a new target gene of miR-302b, FZD6 has the potential to become a prognostic and therapeutic target for OSCC patients.