Mice with a targeted deletion of parathyroid hormone (PTH)-related peptide (PTHrP) develop a form of dyschondroplasia resulting from diminished proliferation and precocious maturation of chondrocytes. The hypertrophic zone of the mutant epiphyseal cartilage revealed aberrant heterogeneous populations of chondrocytes, i.e., non-hypertrophic cells at different stages of differentiation. Therefore, PTHrP appears to play a central role in modulating cell proliferation and differentiation. The biological function of PTHrP is mediated by signaling pathway linked to the PTH/PTHrP receptor. However, the amino acids at 87-107 positions of PTHrP show a putative nucleolar targeting signal, and thought to involve in the resistance to apoptosis. Chondrocytic cell line, CFK2, transfected with truncated forms of PTHrP cDNA showed this peptide in the nucleoli mediated by translation initiating from AUG-codon and alternatively initiating from CUG codons. Thereby, PTHrP appears to act as a bipartite modulator of chondrocyte proliferation/differentiation, both through signal transduction linked to the PTH/PTHrP receptor and by its direct action in the nucleolus. Meanwhile, PTH/PTHrP receptor expression is controlled by two promoters in mouse, and the downstream promoter acts predominantly in bone and cartilage. We found 1,25-dihydroxyvitamin D3 [1,25 (OH)₂D₃] downregulated the activity of the downstream promoter in osteoblasts, but not in chondrocytes. This indicates that the interplay between PTH and 1,25 (OH)₂D₃ is specific to their overlapping roles of serum calcium regulation in bone, and not to their complementary effects on proliferation/differentiation of chondrocytes. Thus, we will review our recent examinations on cartilage development in conjunction with the biological role in PTHrP, PTH/PTHrP receptor and 1,25 (OH)₂D₃.

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p27, a cyclin-dependent kinase inhibitor, plays an important role in the negative regulation of the cell cycle during G1-S phases. In our laboratory, we examined expressions of p27 and related factors in oral squamous cell carcinoma (OSCC) and adenoid cystic carcinoma (ACC) to discuss the diagnostic and therapeutic significance of p27 and its related factors in oral malignancies. Our studies demonstrated the following : 1. Reduced expression of p27 is observed in 87% of OSCCs and 84% of ACCs. 2. There is a strong correlation between reduced expression of p27 and poor prognosis of patients with OSCC and ACC. 3. Reduced expression of p27 in malignancies may be caused by post-translational ubiquitin-mediated degradation. 4. High expression of Skp2, an F-box protein specific to p27, is correlated with poor prognosis in OSCC and an inverse correlation between the expression of Skp2 and p27 was observed. 5. Proteasome inhibitors induce apoptosis of OSCC cells through p27 accumulation. 6. Transfection of wild and degradation-resistant mutant types of the p27 gene inhibits the growth of OSCC cells. These results indicate that p27 and its related factors play important roles in the development of OSCC and can be novel therapeutic targets for oral malignancies as well as strong prognostic markers.

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It is well known that peptide growth factors play important roles in skeletal myogenesis. It is also known that tongue striated muscles have several unique characteristics not found in other skeletal muscles, such as limb and trunk muscles, implying that roles of growth factors in tongue myogenesis differ from those in the myogenesis of limb and trunk. Thus, we have studied the roles of insulin-like growth factors (IGFs), hepatocyte growth factor (HGF), and transforming growth factor α (TGFα) in mouse tongue myogenesis. IGF-I promotes the differentiation of tongue myoblasts. HGF promotes the migration and proliferation of tongue myogenic cells, but it inhibits the differentiation of tongue myoblasts. TGFα promotes the differentiation of tongue myoblasts. The roles of IGF-I and HGF in tongue myogenesis seem to be almost identical to those in the myogenesis of limb and cultured myogenic cell lines, such as C2 and L6 ; on the other hand, the role of TGFα seems to differ from them. It is still unknown if the difference in the role of TGFα is ascribed or related to the unique characteristics of tongue striated muscles.

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The psychophysiological effects of gumchewing were studied by event-related potential (ERP) in 12 healthy volunteers (six males and six females) aged 20-57 years. ERP was recorded with the Ten-twenty electrode system from the contingent negative variation (CNV) paradigm after gumchewing and resting, and 5 event-related potential components (N100, P300, Early CNV, Middle CNV, Rate CNV) were extracted for principle component analysis. N100 peak amplitude after gumchewing was significantly larger than that after resting at F₃, F_Z, F₇ and F₈ (p<0.05). Early CNV amplitude after gumchewing was significantly larger than that after resting at F_Z, F₇, C₄, P₃, T₆ and O₂ (p<0.05). Reaction time after gumchewing was significantly shorter than that after resting. These results suggested that gumchewing raises general attention and the arousal level with precision.

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Many reports have regarded Caiman as a very important topic in the study of comparative anatomy, because this creature is a very attractive and significant animal, especially in oral science. It has been made clear by analyzing the structures of Caiman's tooth enamel and dentine that Caiman is in a transitional stage in evolution from amphibia to mammalia, morphologically. However, neither the structure nor the development of its periodontal tissue has been clarified so far.
In this investigation, the fine structure of Caiman crocodilus tooth cementum was observed by using light and electron microscopy, in order to clarify the functions of human periodontal tissue, morphologically.
The findings indicated that there are at least two layers in Caiman crocodilus cementum, which are named the inner layer of cementum (ILC) and the outer layer of cementum (OLC) in this paper. The ILC is much more mineralized than the OLC and the extrinsic fibers which mainly comprise the ground substance in both layers were revealed. Moreover, there are many cells in the cementum, which are confirmed cementocytes derived from mesenchyme and the epithelial rests of Malassez. Caiman crocodilus tooth cementum still has many primitive features, but has the fundamental structure to play a functional role as human tooth cementum, morphologically.

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