Wnt/β-catenin Promotes Cementum Apposition in Periodontal Regeneration.

Regeneration of periodontal tissue, particularly the cementum-periodontal ligament (PDL)-bone complex, has long been challenging because the differentiation kinetics of cells and the molecular pathways contributing to the regeneration process are largely unknown. We aimed to evaluate the cell behavior and molecular pathways that contribute to periodontal tissue regeneration in vivo. We analyzed the process of periodontal tissue regeneration through subrenal capsule transplantation of immediately extracted molars in mice.

Homozygosity for a Rare Variant Suggests a Contributory Role in Congenital Insensitivity to Pain.

Congenital insensitivity to pain is a rare human condition in which affected individuals do not experience pain throughout their lives. This study aimed to identify the molecular etiology of congenital insensitivity to pain in two Thai patients. Clinical, radiographic, histopathologic, immunohistochemical, and molecular studies were performed.

Genetic Variants in Are Associated with Isolated Dental Anomalies.

KCTD1 plays crucial roles in regulating both the SHH and WNT/β-catenin signaling pathways, which are essential for tooth development. The objective of this study was to investigate if genetic variants in might also be associated with isolated dental anomalies. We clinically and radiographically investigated 362 patients affected with isolated dental anomalies.

Loss of Autophagy Disrupts Stemness of Ameloblast-Lineage Cells in Aging.

Autophagy is one of the intracellular degradation pathways and maintains cellular homeostasis, regulating the stress response, cell proliferation, and signal transduction. To elucidate the role of autophagy in the maintenance of dental epithelial stem cells and the subsequent enamel formation, we analyzed autophagy-deficient mice in epithelial cells (Atg7;KRT14-Cre mice), focusing on the influence of aging and stress environments. We also performed in vitro cell and organ culture experiments with an autophagy inhibitor.

A Mutation in Is Associated with Multiple Supernumerary Cusps and Root Maldevelopment.

Background: Enamel knots and Hertwig epithelial root sheath (HERS) regulate the growth and folding of the dental epithelium, which subsequently determines the final form of tooth crown and roots. We would like to investigate the genetic etiology of seven patients affected with unique clinical manifestations, including multiple supernumerary cusps, single prominent premolars, and single-rooted molars.

Methods: Oral and radiographic examination and whole-exome or Sanger sequencing were performed in seven patients.

Rare Variants in Are Associated with Mesiodens, Root Maldevelopment, and Oral Exostoses in Humans.

Background: Low density lipoprotein receptor-related protein 4 (LRP4; MIM 604270) modulates WNT/β-catenin signaling, through its binding of WNT ligands, and to co-receptors LRP5/6, and WNT inhibitors DKK1, SOSTDC1, and SOST. LRP4 binds to SOSTDC1 and WNT proteins establishing a negative feedback loop between Wnt/β-catenin, Bmp, and Shh signaling during the bud and cap stages of tooth development. Consistent with a critical role for this complex in developing teeth, mice lacking or have multiple dental anomalies including supernumerary incisors and molars.

CACNA1S mutation-associated dental anomalies: A calcium channelopathy.

Objectives: To identify the molecular etiology of distinct dental anomalies found in eight Thai patients and explore the mutational effects on cellular functions.

Materials And Methods: Clinical and radiographic examinations were performed for eight patients. Whole exome sequencing, mutant protein modelling, qPCR, western blot analysis, scratch assays, immunofluorescence, confocal analysis, in situ hybridization, and scanning electron micrography of teeth were done.

Ift88 regulates enamel formation via involving Shh signaling.

Objectives: The ciliopathies are a wide spectrum of human diseases, which are caused by perturbations in the function of primary cilia. Tooth enamel anomalies are often seen in ciliopathy patients; however, the role of primary cilia in enamel formation remains unclear.

Materials And Methods: We examined mice with epithelial conditional deletion of the ciliary protein, Ift88, (Ift88 ;K14Cre).

Perivascular Hedgehog responsive cells play a critical role in peripheral nerve regeneration via controlling angiogenesis.

Hh signaling has been shown to be activated in intact and injured peripheral nerve. However, the role of Hh signaling in peripheral nerve is not fully understood. In the present study, we observed that Hh signaling responsive cells [Gli1(+) cells] in both the perineurium and endoneurium.

Expression of R-spondins/Lgrs in development of movable craniofacial organs.

Wnt signaling plays a critical role in the development of many organs, including the major movable craniofacial organs tongue, lip, and eyelid. Four members of the R-spondin family (Rspo1-4) bind to Lgr4/5/6 to regulate the activation of Wnt signaling. However, it is not fully understood how Rspos/Lgrs regulate Wnt signaling during the development of movable craniofacial organs.

A novel P3H1 mutation is associated with osteogenesis imperfecta type VIII and dental anomalies.

Objective: Our objective was to investigate the molecular etiology of osteogenesis imperfecta type VIII and dental anomalies in 4 siblings of a Karen tribe family.

Materials And Methods: Four patients and their unaffected parents were studied by clinical and radiographic examination. In situ hybridization of P3h1 during early murine tooth development, whole-exome sequencing, and Sanger direct sequencing were performed.

MicroRNAs regulate distal region of mandibular development through Hh signaling.

Mandibular anomalies are often seen in various congenital diseases, indicating that mandibular development is under strict molecular control. Therefore, it is crucial to understand the molecular mechanisms involved in mandibular development. MicroRNAs (miRNAs) are noncoding small single-stranded RNAs that play a critical role in regulating the level of gene expression.

Overactivation of the NF-κB pathway impairs molar enamel formation.

Objective: Hypohidrotic ectodermal dysplasia (HED) is a hereditary disorder characterized by abnormal structures and functions of the ectoderm-derived organs, including teeth. HED patients exhibit a variety of dental symptoms, such as hypodontia. Although disruption of the EDA/EDAR/EDARADD/NF-κB pathway is known to be responsible for HED, it remains unclear whether this pathway is involved in the process of enamel formation.

Juberg-Hayward syndrome is a cohesinopathy, caused by mutation in ESCO2.

Background: Juberg-Hayward syndrome (JHS; MIM 216100) is a rare autosomal recessive malformation syndrome, characterized by cleft lip/palate, microcephaly, ptosis, short stature, hypoplasia or aplasia of thumbs, and dislocation of radial head and fusion of humerus and radius leading to elbow restriction.

Objective: To report for the first time the molecular aetiology of JHS.

Patient And Methods: Clinical and radiographic examination, whole exome sequencing, Sanger sequencing, mutant protein model construction, and in situ hybridization of Esco2 expression in mouse embryos were performed.

Gli3 is a Key Factor in the Schwann Cells from Both Intact and Injured Peripheral Nerves.

Hedgehog (Hh) signaling has been shown to be involved in regulating both intact and injured peripheral nerves. Therefore, it is critical to understand how Hh signaling is regulated in the peripheral nerve. One of the transcription factors of the Hh signaling pathway, Gli3, functions as both a repressor and an activator of Hh signaling activity.

R2TP/PAQosome as a promising chemotherapeutic target in cancer.

R2TP/PAQosome (particle for arrangement of quaternary structure) is a novel multisubunit chaperone specialized in the assembly/maturation of protein complexes that are involved in essential cellular processes such as PIKKs (phosphatidylinositol 3-kinase-like kinases) signaling, snoRNP (small nucleolar ribonucleoprotein) biogenesis, and RNAP II (RNA polymerase II) complex formation. In this review article, we describe the current understanding of R2TP/PAQosome functions and characteristics as well as how the chaperone complex is involved in oncogenesis, highlighting DNA damage response, mTOR (mammalian target of rapamycin) pathway as well as snoRNP biogenesis. Also, we discuss its possible involvement in HNSCC (head and neck squamous cell carcinoma) including OSCC (oral squamous cell carcinoma).

Molecular mechanisms in palatal rugae development.

Background: Periodic patterning of iterative structures is diverse across the animal kingdom. Clarifying the molecular mechanisms involved in the formation of these structures helps to elucidate the genetic commonality of developmental processes, as organs with these structures are believed to share the same molecular mechanisms and fundamental processes. Palatal rugae are periodic corrugated structures on the hard palate and are conserved in all mammals.

Ift88 is involved in mandibular development.

The mandible is a crucial organ in both clinical and biological fields due to the high frequency of congenital anomalies and the significant morphological changes during evolution. Primary cilia play a critical role in many biological processes, including the determination of left/right axis patterning, the regulation of signaling pathways, and the formation of bone and cartilage. Perturbations in the function of primary cilia are known to cause a wide spectrum of human diseases: the ciliopathies.

Primary cilia in murine palatal rugae development.

Periodic patterning of iterative structures is a fundamental process during embryonic development, since these structures are diverse across the animal kingdom. Therefore, elucidating the molecular mechanisms in the formation of these structures promotes understanding of the process of organogenesis. Periodically patterned ridges, palatal rugae (situated on the hard palate of mammals), are an excellent experimental model to clarify the molecular mechanisms involved in the formation of periodic patterning of iterative structures.

Bmp signaling in molar cusp formation.

Tooth cusp is a crucial structure, since the shape of the molar tooth is determined by number, shape, and size of the cusp. Bone morphogenetic protein (Bmp) signaling is known to play a critical role in tooth development, including in initiation. However, it remains unclear whether Bmp signaling is also involved in cusp formation.

Ift88 limits bone formation in maxillary process through suppressing apoptosis.

Objective: The development of the maxillary bone is under strict molecular control because of its complicated structure. Primary cilia play a critical role in craniofacial development, since defects in primary cilia are known to cause congenital craniofacial dysmorphologies as a wide spectrum of human diseases: the ciliopathies. The primary cilia also are known to regulate bone formation.

Semaphorin 3A Inhibits Nerve Regeneration During Early Stage after Inferior Alveolar Nerve Transection.

Neuroma formation at sites of injury can impair peripheral nerve regeneration. Although the involvement of semaphorin 3A has been suggested in neuroma formation, this detailed process after injury is not fully understood. This study was therefore undertaken to examine the effects of semaphorin 3A on peripheral nerve regeneration during the early stage after injury.

ADAMTSL1 and mandibular prognathism.

Mandibular prognathism is characterized by a prognathic or prominent mandible. The objective of this study was to find the gene responsible for mandibular prognathism. Whole exome sequencing analysis of a Thai family (family 1) identified the ADAMTSL1 c.