Bone remodeling, comprising resorption of existing bone and de novo bone formation, is required for the maintenance of a constant bone mass. Prostaglandin (PG)E 2 promotes both bone resorption and bone formation. By infusing PGE 2 to mice lacking each of four PGE receptor (EP) subtypes, we have identified EP4 as the receptor that mediates bone formation in response to this agent. Consistently, bone formation was induced in wild-type mice by infusion of an EP4-selective agonist and not agonists specific for other EP subtypes. In culture of bone marrow cells from wild-type mice, PGE2 induced expression of core-binding factor ␣1 (Runx2͞Cbfa1) and enhanced formation of mineralized nodules, both of which were absent in the culture of cells from EP4-deficient mice. Furthermore, administration of the EP4 agonist restored bone mass and strength normally lost in rats subjected to ovariectomy or immobilization. Histomorphometric analysis revealed that the EP4 agonist induced significant increases in the volume of cancellous bone, osteoid formation, and the number of osteoblasts in the affected bone of immobilized rats, indicating that activation of EP4 induces de novo bone formation. In addition, osteoclasts were found on the increased bone surface at a density comparable to that found in the bone of control animals. These results suggest that activation of EP4 induces bone remodeling in vivo and that EP4-selective drugs may be beneficial in humans with osteoporosis.B ones undergo continuous remodeling through repeated cycles of destruction and rebuilding (1). This remodeling is mediated by the well balanced actions of osteoclasts, which resorb old bones, and osteoblasts, which form new bones. However, in the elderly, especially in postmenopausal women, the extent of bone resorption far exceeds that of bone rebuilding, resulting in osteoporosis and the associated increases in bone fragility and susceptibility to fractures (2). About 100 million people are estimated to suffer from this debilitating disease worldwide. Several drugs have been developed to treat osteoporosis, with most inhibiting bone resorption and only a few promoting bone formation (3). Such modulation of only one of the two processes in bone remodeling renders these drugs of limited efficacy in restoring the normal balance and bone mass.Recently, significant advances have been made in our understanding of molecular mechanisms of osteoclast and osteoblast differentiation (4), but such knowledge has not been exploited fully to develop a drug that corrects the imbalance and restores normal bone remodeling. Prostaglandins (PGs) are a group of lipid mediators that are produced from arachidonic acid in a variety of tissues under various physiological and pathophysiological conditions and serve to maintain local homeostasis (5). Among them, PGs of the E type work bimodally in bone metabolism (6). PGE 2 potently induces bone resorption in bone organ cultures, whereas repeated injection of this compound in vivo induces bone formation in a variety of animals includ...

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CD82/KAI1, a member of the tetraspanin superfamily, is a suppressor of metastasis and CD82 inhibits canonical Wnt signaling via downregulation of several Frizzled (FZD) isoforms, resulting in accumulation of β-catenin at the cell membrane. In this study, we investigated the mechanism through which CD82 inhibited FZD expression by examining the effects of microRNAs (miRNAs). The miRanda algorithm predicted 11 miRNAs from FZD sequences. Among these miRNAs, CD82 caused upregulation of miR-203 (by 2.095-fold) and downregulation of miR-338-3p (by 0.354-fold) as compared with control cells. Transfection with miR-203 and miR338-3p mimics or inhibitors revealed that miR-203 downregulated FZD2 mRNA (by 0.268-fold) and protein expression (by 0.701-fold). Moreover, transfection with the miR-203 mimic also inhibited cell migration. Therefore, these findings suggested that CD82 enhanced the expression of miR-203 and directly downregulate FZD2 expression, suppressing cancer metastasis by inhibition of the Wnt signaling pathway.

This article highlights several refractory oral diseases, such as stomatitis, burning mouth syndrome (BMS), glossalgia, atypical facial pain (AFP), oral cancer, dry mouth, and Sjögren's syndrome (SJS), in which use of Japanese herbal medicines, Kampo medicines (KM), on the basis of Kampo theory could exert the maximum effects on human body. (1) In acute stomatitis, heat because of agitated vital energy may affect the head, chest, and middle abdominal region. Stomatitis is also related to the generation of reactive oxygen species (ROS). There are many antioxidants in the crude extracts of KM. Thus, we can control environmental factors (cold, heat, dampness, dryness) and vital energy, blood, and fluid of the organ systemically using KM to treat stomatitis and eliminate local ROS accumulation. (2) BMS, glossalgia, and AFP are multifactorial syndromes involving the interaction of biological and psychological factors. Local temperature decrease and edema often occur in chronic pain. These are local circulatory disturbances that can be resolved by improving the flow of blood and fluid. Several KM, such as Tokishakuyakusan and Kamishoyosan (KSS), are effective for enhancing peripheral circulation. Those such as Saikokaryukotuboreito, Yokukansan, KSS, and Saibokutou can reduce stress and associated pain by altering glutamatergic and monoaminergic transmission in the brain. The clinical efficacy of KM for BMS and AFP may depend on the regulation of the mesolimbic dopaminergic and descending glutamatergic pain modulation systems. (3) Regarding oral cancer treatment, I introduce four possible applications of KM, inhibition of the proliferation of cancer cells, complementation of the main cancer therapy, reduction of side effect caused by the main anti-cancer therapy and improvement of quality of life such as the overall status and/or oral discomfort. This review explains in more details Hozai such as Hochuekkito (HET), Juzendaihoto, and Ninjinyoeito (NYT) that are frequently used to improve both immunosuppression and deficiencies of Ki, Ketsu, and Sui in oral cancer patients. (4) Heat- and cold-dryness stages exist in dry mouth and SJS. Byakkokaninjinto is useful for heat-dryness, while NYT, Bakumondoto, and HET have moisturizing effects in the cold-dryness stage. Thus, Kampo therapy is useful for many oral diseases that cannot be cured by western medicine.