Kampo Therapies and the Use of Herbal Medicines in the Dentistry in Japan.

Dental caries and periodontal disease are two major diseases in the dentistry. As the society is aging, their pathological meaning has been changing. An increasing number of patients are displaying symptoms of systemic disease and so we need to pay more attention to immunologic aggression in our medical treatment. For this reason, we focused on natural products. Kampo consists of natural herbs-roots and barks-and has more than 3000 years of history. It was originated in China as traditional medicine and introduced to Japan. Over the years, Kampo medicine in Japan has been formulated in a way to suit Japan's natural features and ethnic characteristics. Based on this traditional Japanese Kampo medicine, we have manufactured a Kampo gargle and Mastic Gel dentifrice. In order to practically utilize the effectiveness of mastic, we have developed a dentifrice (product name: IMPLA CARE) and treated implant periodontitis and severe periodontitis.

High concentration of sodium butyrate suppresses osteoblastic differentiation and mineralized nodule formation in ROS17/2.8 cells.

Periodontitis is a destructive disease that is likely the result of the activities of different microbial complexes, including anaerobic Gram-negative periodontopathic bacteria. Butyric acid (sodium butyrate; BA) is a major metabolic by-product of anaerobic Gram-negative periodontopathic bacteria present in subgingival plaque. This study was undertaken to examine the effect of BA on the expression of osteogenesis-related transcription factors and mineralized nodule formation in osteoblastic ROS17/2.8 cells. The cells were cultured with 0 (control), 10(-5), 10(-4), or 10(-3) M BA for up to 7 days. The gene and protein expression levels of transcription factors such as Runx2, Osterix, Dlx5, Msx2, and AJ18, as well as extracellular matrix proteins such as bone sialoprotein (BSP) and osteocalcin, were examined using real-time PCR and Western blotting, respectively. Mineralized nodule formation was detected by alizarin red staining. The expression of Runx2, Osterix, Dlx5, and Msx2 decreased significantly in the presence of 10(-3 )M BA compared to the control, whereas AJ18 expression increased significantly. Mineralized nodule formation decreased markedly in the presence of 10(-3) M BA. Alkaline phosphatase activity and the expression of bone sialoprotein and osteocalcin decreased significantly in the presence of 10(-3) M BA compared to the control. These results suggest that 10(-3) M BA suppresses osteoblastic differentiation and mineralized nodule formation in ROS17/2.8 cells.

Sodium butyrate stimulates mineralized nodule formation and osteoprotegerin expression by human osteoblasts.

OBJECTIVE: Butyric acid (sodium butyrate; BA) is a major metabolic by-product of main periodontopathic bacteria present in subgingival plaque. In the present study, we examined the effects of BA on cell proliferation, alkaline phosphatase (ALPase) activity, mineralized nodule formation, extracellular matrix protein expression, macrophage colony-stimulating factor (M-CSF), and osteoprotegerin (OPG) in normal human osteoblasts. METHODS: The cells were cultured with 0, 10(-8), 10(-6) or 10(-4)M BA for up to 12 days. Mineralized nodule formation was detected by alizarin red staining, and the calcium content in mineralized nodules was determined using a calcium assay kit. The gene and protein expression levels for type I collagen, bone sialoprotein (BSP), osteopontin (OPN), M-CSF, and OPG were examined using real-time PCR and ELISA, respectively. RESULTS: Mineralized nodule formation and the calcium content of mineralized nodules were increased by BA in a dose-dependent manner. Cell proliferation and ALPase activity were not affected by the addition of BA. Following the addition of 10(-4)M BA, the expression levels of BSP, OPN, and OPG increased, whereas the expression levels of type I collagen and M-CSF were not markedly affected. CONCLUSION: These results suggest that BA stimulates bone formation by increasing the production of BSP and OPN, whereas it suppresses osteoclast differentiation by increasing the production of OPG by human osteoblasts.

Lipopolysaccharide enhances the production of nicotine-induced prostaglandin E2 by an increase in cyclooxygenase-2 expression in osteoblasts.

Previous studies have indicated that lipopolysaccharide (LPS) from Gram-negative bacteria in plaque induces the release of prostaglandin E(2) (PGE(2)), which promotes alveolar bone resorption in periodontitis, and that tobacco smoking might be an important risk factor for the development and severity of periodontitis. We determined the effect of nicotine and LPS on alkaline phosphatase (ALPase) activity, PGE(2) production, and the expression of cyclooxygenase (COX-1, COX-2), PGE(2) receptors Ep1>4, and macrophage colony stimulating factor (M-CSF) in human osteoblastic Saos-2 cells. The cells were cultured with 10(-3) M nicotine in the presence of 0, 1, or 10 mug/ml LPS, or with LPS alone. ALPase activity decreased in cells cultured with nicotine or LPS alone, and decreased further in those cultured with both nicotine and LPS, whereas PGE(2) production significantly increased in the former and increased further in the latter. By itself, nicotine did not affect expression of COX-1, COX-2, any of the PGE(2) receptors, or M-CSF, but when both nicotine and LPS were present, expression of COX-2, Ep3, Ep4, and M-CSF increased significantly. Simultaneous addition of 10(-4) M indomethacin eliminated the effects of nicotine and LPS on ALPase activity, PGE(2) production, and M-CSF expression. Phosphorylation of protein kinase A was high in cells cultured with nicotine and LPS. These results suggest that LPS enhances the production of nicotine-induced PGE(2) by an increase in COX-2 expression in osteoblasts, that nicotine-LPS-induced PGE2 interacts with the osteoblast Ep4 receptor primarily in autocrine or paracrine mode, and that the nicotine-LPS-induced PGE(2) then decreases ALPase activity and increases M-CSF expression.