Recently, peptides have been used as an option for rational drug design. We focus on the peptide antagonist, WP9QY (W9) peptide, which was originally designed to mimic the critical binding site of a tumor necrosis factor (TNF)-α on TNF receptor type 1 using a molecular modeling technique. Here, the inhibitory effect of the W9 peptide on inflammatory bone resorption is reviewed, including its peptide delivery system, which could be a tool for overcoming the aggregation problem of peptide drugs in clinical applications.

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Dentin sialophosphoprotein (DSPP) is critical for proper mineralization of tooth dentin, and understanding its structure and function should yield important insights into how dentin biomineralization is controlled. During the recent six years, DSPP-derived proteins isolated from developing porcine teeth have been characterized. Porcine DSPP is expressed and secreted by odontoblasts and is processed by BMP-1, MMP-20 and MMP-2 into three main parts: dentin sialoprotein (DSP), dentin glycoprotein (DGP), and dentin phosphoprotein (DPP). We have learned that DSP is a proteoglycan that forms covalent dimers, DGP is a phosphorylated glycoprotein, and DPP is a highly phosphorylated intrinsically disordered protein that shows extensive length polymorphisms due to the genetic heterogeneity of its coding region.

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To investigate the role of transforming growth factor-β (TGF-β) in regulating the fate of cranial neural crest cells (CNC) during mandibular and tooth development, we generated mutant mice with tissue-specific Tgfbr2 gene ablation using a Cre/loxP recombination system exclusively in the cranial neural crest lineage (Tgfbr2^fl/fl; Wnt1-Cre). Tgfbr2^fl/fl; Wnt1-Cre mice show mandible defects including the abnormal shape of Meckel’s cartilage, a small mandibular bone, and perturbed chondrogenesis in the proximal region of the mandible. TGF-β signaling stimulates the proliferative activity of chondrocytes in Meckel’s cartilage through Ctgf and of osteoblasts in mandibular bone through Msx1 expression. Interestingly, in the proximal region of Tgfbr2^fl/fl; Wnt1-Cre mice, cartilage was replaced by bone formation as a result of accelerated osteoblast differentiation due to elevated Runx2 and Dlx5 expression in osteo-chondroprogenitor cells. Additionally, the deletion of Dlx5 in Tgfbr2^fl/fl; Wnt1-Cre mice resulted in the rescue of cartilage formation in the angular processes. Regarding tooth development, Tgfbr2^fl/fl; Wnt1-Cre mice showed abnormal dentin formation. Following kidney capsule transplantation, Tgfbr2 mutant tooth germs exhibited defects, with a decreased dentin thickness and absent dentinal tubules. The expression of ColI and Dsp was reduced. In addition, the expression of the intermediate filament nestin was decreased in Tgfbr2^fl/fl; Wnt1-Cre mouse samples. This suggests that TGF-β signaling controls odontoblast maturation and dentin formation during tooth development. In this review, we reveal these mandibular and tooth phenotypes in Tgfbr2^fl/fl; Wnt1-Cre, and discuss the intrinsic requirement of TGF-β signaling during craniofacial development.

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A number of gene mutations are known to cause human syndromes that involve oral defects. Among them, mutations of either EVC or EVC2 genes are known to be responsible for Ellis-van Creveld (EvC) syndrome. Oral anomalies of EvC syndrome are characterised by multiple frenula, congenital missing teeth, and abnormal tooth morphogenesis including a conical shape and enamel hypoplasia. Patients with EvC have skeletal defects and nail dysplasia, and often also show cardiac defects. Evc protein localises at the basal body of the primary cilium, where Hedgehog signalling is mediated, and cells lacking Evc exhibit a diminished response to the Hedgehog agonist purmorphamine. The dental anomalies noted in patients with EvC syndrome and mouse Evc mutants add further evidence supporting the important role of the primary cilium during tooth development.

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Bacteriocins are antimicrobial peptides or proteins produced by bacteria. Lantibiotics are a class of bacteriocin produced by gram-positive bacteria that are characterized by the presence of unusual amino acids in their structure. Due to their unique properties, lantibiotics have recently attracted significant attention as new antimicrobial agents to combat infectious disease. Nisin is a well-studied prototype lantibiotic with high potentiality, significant physicochemical stability, and no known human toxicity. It targets lipid II and uses it as a docking molecule. It is effective against drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Herein, the author describes the specific features of lantibiotics, mainly nisin, with regard to their biosynthesis and mode of action, and also highlights the application of lantibiotics in the medical field and in the control of dental disease.

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We examined changes in dental attrition levels by sex and age group among Japanese people in the Jomon (16,000 BP-2,300 BP) and Edo (1603-1868 AD) periods. We discuss here the changes in attrition by time period and the changes in diet which could be speculated based on such changes in attrition. In the Jomon people, attrition advanced rapidly from early middle age and became considerable in late middle to older age. In the Edo people, attrition occurred to a much lesser degree. Skeletal remains from the Edo period indicate that attrition was more advanced in late middle age and the elderly than in early middle age; however, the advancement of attrition was gradual, and the attrition level was not as considerable as in the Jomon people. From these results, it can be predicted that attrition levels differed in Japanese people over time and that the differences in attrition levels decreased between early middle age and late middle age and the elderly.

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