Statins are a class of drugs widely used in the treatment of cardiovascular diseases to reduce hypercholesterolemia, and involve an increased prevalence of osteoporosis. Several studies suggested that statin mediates stimulation of bone remodeling. One of the statin family members was first isolated from Penicillin citrium (mevastatin), and another later from Aspergillus terreus (lovastatin). Roles of statins are mediated by competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, such as inhibition of the mevalonate pathway. Statins have a potential antiinflammatory effect (IL-6), which may be related to promotion of bone growth and maintaining bone health. Statins in local use and general administration enhance osteoblastic differentiation and production of bone matrix proteins via bone morphogenetic protein 2 (BMP-2) signaling pathways. Clinical applications of statins have increasingly been reported for bone fractures and implant dentistry. The present review introduces biophysiological functions of the statin family in normal remodeling of bone tissues demonstrated by both in vivo and in vitro studies, and in promoting bone growth caused by osteoprotegerin production by statins with BMP-2.

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Epithelial dysplasia and carcinoma in-situ (CIS) of the oral mucosa are two different borderline grades similar to each other, and it is difficult for pathologists to distinguish these two lesions on hematoxylin and eosin-stained sections only. To support objective differential diagnoses, we have developed a new computer-aided analysis system. The method was based on a comparison of the elevation levels in the drop shape between twin-pairs of neighboring rete ridges. The dissimilarity of the drop shape was defined by the roundness difference between a pair of rete ridge units. All the steps were performed using a graphical user interface. The similarity levels in epithelial dysplasia were higher than those in CIS, whose histopathological diagnoses were conventionally made by experienced pathologists. The developed image processing method showed good promise for the computer-aided pathological assessment of oral borderline malignancies in clinical practice.

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p16^INK4A is a cell cycle-related factor that has been identified as a tumor suppressor in various types of human cancer. Using immunohistochemical and fluorescent in situ hybridization (FISH) analyses, we undertook a study of p16^INK4A in 40 cases of ameloblastoma. Immunohistochemically, when considering the level of expression of the p16^INK4A protein, the cases which were positive for p16^INK4A (mainly the follicular type) had a tendency to recur. Plexiform type in our series had a low tendency to recur and a low or absent p16^INK4A expression in protein level. In the relationship between the expression of p16^INK4A protein and histological types, the plexiform type showed a high negative rate of p16^INK4A protein, compared with the follicular and acanthomatous types. Using FISH analysis, we found that signals of p16^INK4A and chromosome 9 generally showed both diploid patterns in all cases and in all histological types. We estimated that ameloblastoma would reveal that p16^INK4A expression was absent in genetic alteration of the p16^INK4A gene.

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The purpose of this study was to evaluate the responses of immature young pulp cells under conditions of hypoxia with or without reoxygenation. Proliferative activity and bone related protein mRNAs were evaluated. Proliferation ratios in the hypoxia only and hypoxia with reoxygenation groups were significantly lower than those in the control group on days 2 and 3. On day 4, there was no significant difference between the control and the reoxygenation group. There was no significant difference in alkaline phosphatase (ALP) mRNA among the control, hypoxia and reoxygenation groups at any of the time periods. Expression of dentinsialophosphoprotein (DSPP) mRNA was significantly lower in the hypoxia group than in the control and the reoxygenation group on days 2 and 3. Hypoxic condition suppressed the expression of a gene specific to odontoblasts in immature young pulp cells, suggesting that it affects the differentiation ability of odontoblasts.

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A case of radicular cyst with actinomycosis in a 36-year-old man is described. The cyst, a well-circumscribed radiolucent lesion in the anterior region of the maxilla, was first noticed by the patient's dentist. Computed tomography indicated a cystic area with low density, which included the roots of upper lateral teeth, and revealed a root fracture of the right central incisor. The surgically-removed sample was histopathologically diagnosed as radicular cyst. In addition to usual histological findings of its cyst wall, the cyst was shown to contain actinomycotic flora, which is extremely rare. In the literature, 13 cases of actinomycosis in odontogenic cysts have been documented. Their clinicopathological features, together with those of our case, were reviewed. They involved mainly the maxilla, and the male/female ratios were almost equal. All of the cases were extirpated by conventional surgery. Although their clinical courses were mostly uneventful, bacterial infection occasionally led to aggressive and locally destructive changes.

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Central giant cell granuloma (CGCG) is a non-neoplastic proliferative lesion of unknown etiology. A wide variety of conditions could be misdiagnosed with CGCG, both histopathologically and radiographically. We report a rare case involving a 40-year-old female with CGCG of the mandible and prominent osteoblastic differentiation unlike that of conventional CGCG common to osteosarcoma. The patient presented with a painless swelling in the area between the lower left canine to the lower first molar. The lesion was surgically removed under general anesthesia, and the surgical specimen was investigated histopathologically and immunohistochemically. In this lesion, multinucleated giant cells were dispersed among a highly cellular stroma consisting of mononuclear round and spindle-shaped cells. Mononuclear cells demonstrated cellular pleomorphism and high proliferative activity, as evidenced by Ki-67 immunostaining. Immature osteoid was seen throughout the lesion, and most mononuclear cells exhibited Runx2 positivity. Despite these histopathological features in common with those of osteosarcoma, the lesion was shown radiographically to be well-defined and without infiltration of the surrounding bone, and a 3-year follow-up of the patient has thus far been uneventful. The lesion was diagnosed as a rare CGCG with prominent osteoblastic differentiation mimicking osteosarcoma.

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