The dynamin inhibitor dynasore inhibits bone resorption by rapidly disrupting actin rings of osteoclasts.

The cytoskeletal organization of osteoclasts is required for bone resorption. Binding of dynamin with guanosine triphosphate (GTP) was previously suggested to be required for the organization of the actin cytoskeleton. However, the role of the GTPase activity of dynamin in the organization of the actin cytoskeleton as well as in the bone-resorbing activity of osteoclasts remains unclear. This study investigated the effects of dynasore, an inhibitor of the GTPase activity of dynamin, on the bone-resorbing activity of and actin ring formation in mouse osteoclasts in vitro and in vivo. Dynasore inhibited the formation of resorption pits in osteoclast cultures by suppressing actin ring formation and rapidly disrupting actin rings in osteoclasts. A time-lapse image analysis showed that dynasore shrank actin rings in osteoclasts within 30 min. The intraperitoneal administration of dynasore inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced trabecular bone loss in mouse femurs. These in vitro and in vivo results suggest that the GTPase activity of dynamin is critical for the bone-resorbing activity of osteoclasts and that dynasore is a seed for the development of novel anti-resorbing agents.

Binding of collagen gene products with titanium oxide.

Titanium is the only metal to which osteoblasts can adhere and on which they can grow and form bone tissue in vivo, resulting in a strong bond between the implant and living bone. This discovery provides the basis for the universal medical application of Ti. However, the biochemical mechanism of bond formation is still unknown. We aimed to elucidate the mechanism of bond formation between collagen, which constitutes the main organic component of bone, and TiO2, of which the entire surface of pure Ti is composed. We analysed the binding between the soluble collagen and TiO2 by chromatography with a column packed with Ti beads of 45 µm, and we explored the association between collagen fibrils and TiO2 (anatase) powders of 0.2 µm. We ran the column of chromatography under various elution conditions. We demonstrated that there is a unique binding affinity between Ti and collagen. This binding capacity was not changed even in the presence of the dissociative solvent 2M urea, but it decreased after heat denaturation of collagen, suggesting the contribution of the triple-helical structure. We propose a possible role of periodically occurring polar amino acids and the collagen molecules in the binding with TiO2.

Advanced alveolar bone resorption treated with implants, guided bone regeneration, and synthetic grafting: a case report.

PURPOSE: To present a vertical ridge augmentation with a composite synthetic bone graft by the mixed bone-filling materials and autogenous bone chips retrieved from the implant osteotomy site for a case for esthetic implant prosthesis on the atrophied alveolar bone. MATERIALS: Nonresorbable and resorbable hydroxyapatite and demineralized freeze-dried bone allograft particles were used at ratio of 1:2:2 (volume ratio). Titanium micromesh was used for alveolar ridge configuration and retention. After 8 months, implant placement and interimplant bone augmentation were performed. RESULTS: 15-mm vertical and 10-mm horizontal bone augmentation has been achieved. Marginal bone heights and periimplant mucosa remained stable in cases of loading after >4 years of follow-up. CONCLUSION: These results suggest that this method has the potential for use in esthetic implant rehabilitation on the highly atrophied alveolar bone.

Phosphorylated chitin increased bone formation when implanted into rat calvaria with the Ti-device.

BACKGROUND: Previously we found that a group of phosphorylated proteins (SIBLINGs) in bone binds with the Ti-device, and increases the early bone formation around the Ti-implants remarkably. From these results, we explained the biochemical mechanism of a strong bond between living bone and Ti, which was discovered by Brånemark and colleagues. For the clinical application of our findings, we need a large amount of these proteins or their substitutes. OBJECTIVE: We aimed to create a new molecule that equips with essential functions of SIBLINGs, Ti-binding, and bone enhancement around the Ti implant. METHODS: We chemically phosphorylated chitin and obtained a soluble form of phosphorylated chitin (P-chitin). In this solution, we immersed the Ti-devices of web-form (TW) which we previously developed and obtained the P-chitin coated TWs. Then we tested the P-chitin coated TWs for their calcification ability in vitro, and bone enhancing ability in vivo, by implanting them into rat calvaria. We compared the P-chitin coated TW and the non-coated TW in regard to their calcification and bone enhancing abilities. RESULTS: Ti-devices coated with phosphorylated-chitin induced a ten times higher calcification in vitro at 20 days, and four times more elevated amount of bone formation in vivo at two weeks than the uncoated Ti-device. CONCLUSIONS: Phosphorylated chitin could be a partial substitute of bone SIBLING proteins and are clinically applicable to accelerate bone formation around the Ti implants, thereby achieving the strong bond between living bone and Ti.

Exposure to Dental Filling Materials and the Risk of Dementia: A Population-Based Nested Case Control Study in Taiwan.

When studying the range of toxic substances triggering dementia, special attention should be paid to the materials used in dental practice, particularly to dental fillings containing amalgam. This necessitated conducting large-scale epidemiologic studies. The aim of our research was to determine the risk factors for developing dementia when filling materials containing amalgam are used in dental practice. In order to achieve the set goals, the following tasks were undertaken: (1) The social and demographic characteristics of the examined patients were studied; (2) the spectrum of concomitant somatic diseases was determined in patients of different gender and age; and (3) the relationship between dementia incidence and the volume of dental filling material containing amalgam was identified in patients with different somatic diseases. In general, the research conducted did not reveal any direct relationship between the development of dementia and the volume of filling material containing amalgam. However, among the people with dementia, there were persons for whom its progression was accelerated in cases where a large volume of dental filling material containing amalgam was present.

RETRACTED: A human chondrogenic cell line retains multi-potency that differentiates into osteoblasts and adipocytes.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the author, Dr. Kimihito Yagami. Dr. Yagami's collaborators Yohei Uyama, Yasumasa Yoshizawa, Saburo Kakuta, Akira Yamaguchi, Masao Nagumo were not involved in the RT-PCR experiments and figure preparation The editor, Sundeep Khosla, was notified by an independent group that specific bands in Figure 3 of the paper appear to be duplicated. This was brought to the attention of the authors. Due to the long interval from the original publication of the paper, the raw data was not available; however, the authors subsequently chose to retract the entire manuscript, and the editor agreed.

Nicotine in cigarettes promotes chromogranin A production by human periodontal ligament fibroblasts.

OBJECTIVE: The body produces chromogranin A (ChgA) in response to stress as an adaptive reaction. While ChgA is used as an index of autonomic nervous system activity, it is also involved in the immunomodulation system, and an increase in its production in patients with periodontal disease and cigarette smokers has been reported. However, its production in periodontal tissue cells subjected to stress and its immunomodulatory action have not been clarified. To investigate the influence of nicotine on periodontal tissue, we measured ChgA production in nicotine-treated periodontal ligament fibroblasts. DESIGN: Using normal human periodontal ligament-derived fibroblasts (HPdLF) as a periodontal tissue model, untreated cells (control) and cells treated with 10 and 100nM nicotine sulfate corresponding to passive and active cigarette smoking, respectively, were cultured for a specific time. The ChgA level in the culture fluid was measured as ChgA production in HPdLF employing ELISA. ChgA gene expression was quantified employing qPCR. In addition, intracellular localisation was confirmed by immunohistochemical staining. RESULTS: In the control HPdLF group, a low level of ChgA was produced, and immunohistochemical ChgA-positive reactions were observed in the nucleus and cytoplasm. In the nicotine-treated HPdLF group, the ChgA mRNA expression level, protein production, and immunostaining-positive rate increased, and the levels were higher in the cells treated with 10nM nicotine corresponding to passive smoking than in the cells treated with 100nM nicotine corresponding to active smoking. CONCLUSION: Human periodontal ligament-derived fibroblasts (HPdLF) produced ChgA, and nicotine increased ChgA production.

Honeycomb form ß-tricalcium phosphate induces osteogenesis by geometrical property with BMSC.

To establish an effective method for bone augmentation, we introduced a new honeycomb-like ß-tricalcium phosphate (H-ß-TCP) with BMP-2 as a scaffold, whose unique geometrical properties induce osteoblastic differentiation of autologous bone marrow mesenchymal stem cells (BMSCs). A total of six beagle dogs from 6 to 7 years old were used for this study. BMSCs were cultured with autologous serum and BMP-2 on H-ß-TCP. Differentiation to osteoblasts was demonstrated in vitro and exo vivo. Scanning electron microscopy revealed formation and calcification of a matrix-like structure within the H-ß-TCP tunnels in BMSC culture. Moreover, treatment of BMP-2 promoted osteoblastic differentiation of BMSCs in H-ß-TCP in a diffusion chamber. These results indicated that H-ß-TCP may be a useful tool for construction of functional artificial bone.

Recombinant human bone morphogenetic protein-2 promotes Indian hedgehog-mediated osteo-chondrogenic differentiation of a human chondrocytic cell line in vivo and in vitro.

We examined osteo-chondrogenic differentiation of a human chondrocytic cell line (USAC) by rhBMP-2 in vivo and in vitro. USAC was established from a transplanted tumor to athymic mouse derived from an osteogenic sarcoma of the mandible. USAC usually shows chondrocytic phenotypes in vivo and in vitro. rhBMP-2 up-regulated not only the mRNA expression of types II and X collagen, but also the mRNA expression of osteocalcin and Cbfa1 in USAC cells in vitro. In vivo experimental cartilaginous tissue formation was prominent in the chamber with rhBMP-2 when compared with the chamber without rhBMP-2. USAC cells implanted with rhBMP-2 often formed osteoid-like tissues surrounded by osteoblastic cells positive for type I collagen. rhBMP up-regulated Ihh, and the expression of Ihh was well correlated with osteo-chondrogenic cell differentiation. These results suggest that rhBMP-2 promotes chondrogenesis and also induces osteogenic differentiation of USAC cells in vivo and in vitro through up-regulation of Ihh.