Bone remodeling is a complex process regulated by several mediators. Recent work has revealed that cytokines and growth factors have significant effects on bone cell metabolism. However, little information is available concerning the production of cytokines during orthodontic tooth movement in human subjects, and there is no non-invasive model for determining the production of cytokines. Therefore, the purpose of this study was to identify and quantify the various cytokines in human gingival crevicular fluid (GCF), and to investigate the changes in their levels during orthodontic tooth movement. Twelve patients (mean age, 14.4 years) were used as subjects. An upper canine of each patient having one treatment for distal movement served as the experimental tooth, whereas the contralateral and antagonistic canines were used as controls. The GCF around the experimental and the two control teeth was taken from each subject immediately before activation, and at 1, 24, and 168 hr after the initiation of tooth movement. Cytokine levels were determined by ELISAs. The concentrations of interleukin (IL)-1 beta, IL-6, tumor necrosis factor-alpha, epidermal growth factor, and beta 2-microglobulin were significantly higher in the experimental group than in the controls at 24 hr after the experiment was initiated. All the cytokines remained at baseline levels throughout the experiment for the two control groups. In contrast to cytokine alteration, the amount of total protein in the GCF exhibited a gradual increase, but no significant difference was observed between the control and experimental groups. Since all cytokines in GCF play an important role in the bone remodeling processes in vitro, the present results indicate that the changes in cytokines in GCF are associated with orthodontic tooth movement.

Prostaglandin E(2) (PGE(2)) enhances osteoclast formation in mouse macrophage cultures treated with receptor activator of nuclear factor-kappaB ligand (RANKL). The effects of PGE(2) on human osteoclast formation were examined in cultures of CD14(+) cells prepared from human peripheral blood mononuclear cells. CD14(+) cells differentiated into osteoclasts in the presence of RANKL and macrophage colony-stimulating factor. CD14(+) cells expressed EP2 and EP4, but not EP1 or EP3, whereas CD14(+) cell-derived osteoclasts expressed none of the PGE(2) receptors. PGE(2) and PGE(1) alcohol (an EP2/4 agonist) stimulated cAMP production in CD14(+) cells. In contrast to mouse macrophage cultures, PGE(2) and PGE(1) alcohol inhibited RANKL-induced human osteoclast formation in CD14(+) cell cultures. H-89 blocked the inhibitory effect of PGE(2) on human osteoclast formation. These results suggest that the inhibitory effect of PGE(2) on human osteoclast formation is mediated by EP2/EP4 signals. SaOS4/3 cells have been shown to support human osteoclast formation in cocultures with human peripheral blood mononuclear cells in response to PTH. PGE(2) inhibited PTH-induced osteoclast formation in cocultures of SaOS4/3 cells and CD14(+) cells. Conversely, NS398 (a cyclooxygenase 2 inhibitor) enhanced osteoclast formation induced by PTH in the cocultures. The conditioned medium of CD14(+) cells pretreated with PGE(2) inhibited RANKL-induced osteoclast formation not only in human CD14(+) cell cultures, but also in mouse macrophage cultures. These results suggest that PGE(2) inhibits human osteoclast formation through the production of an inhibitory factor(s) for osteoclastogenesis of osteoclast precursors.

Maximum occlusal force tended to increase with age. There was a gender difference in the maximum occlusal force at all age groups, values being larger in the males. In the males, the maximum occlusal force continued to increase until their 20s, while in the females, this increase almost terminated at the age of 17.

Inorganic polyphosphates [Poly(P)] are often distributed in osteoblasts. We undertook the present study to verify the hypothesis that Poly(P) stimulates osteoblasts and facilitates bone formation. The osteoblast-like cell line MC 3T3-E1 was cultured with Poly(P), and gene expression and potential mineralization were evaluated by reverse-transcription polymerase chain-reaction. Alkaline phosphatase activity, von Kossa staining, and resorption pit formation analyses were also determined. The potential role of Poly(P) in bone formation was assessed in a rat alveolar bone regeneration model. Poly(P) induced osteopontin, osteocalcin, collagen 1alpha, and osteoprotegerin expression and increased alkaline phosphatase activity in MC 3T3-E1 cells. Dentin slice pit formation decreased with mouse osteoblast and bone marrow macrophage co-cultivation in the presence of Poly(P). Promotion of alveolar bone regeneration was observed locally in Poly(P)-treated rats. These findings suggest that Poly(P) plays a role in osteoblastic differentiation, activation, and bone mineralization. Thus, local poly(P) delivery may have a therapeutic benefit in periodontal disease.

The results suggest that VEGF, FGF-2, and endostatin concentrations are elevated prior to the emergence of HCC and that the distribution of VEGF changes dynamically during the development of HCC.

Summary Membrane cofactor protein (MCP, CD46) is one of the complement regulatory proteins, and is widely distributed in human organs and protects cells from complement-mediated cytotoxicity. We analysed the distribution and the intensities of MCP in liver diseases and evaluated the role of MCP during hepatocarcinogenesis. Western blot analysis revealed that relative densities (density of the sample/density of the standard sample) of MCP in 27 HCC, 18 liver cirrhosis, nine chronic hepatitis and 12 normal liver were 0.63 ± 0.23, 0.21 ± 0.07, 0.25 ± 0.10 and 0.11 ± 0.03 (mean ± s.d.) respectively. MCP expression in hepatocellular carcinoma (HCC) was significantly higher than that in both liver cirrhosis and chronic hepatitis (P < 0.01). The difference in the tumour sizes, the grades of differentiation and viral marker status did not affect the expression. Immunohistological analysis revealed that MCP was distributed mainly in the basolateral membrane of the hepatic cord in non-cancerous liver, along with endothelial cells and bile duct cells. In HCC, the protein was observed on the membrane in a non-polarized fashion. These data suggest that HCC cells acquire the increased MCP expression in a development of HCC and may escape from tumour-specific complement-mediated cytotoxicity.

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An incremental positivity of telomerase was observed during hepatocarcinogenesis. The use of this assay in 21-G-needle biopsy specimens may be useful in clinical examination.