1,720,967 research outputs found

    Etidronate inhibits osteoclast adhesion to bone surfaces but does not interfere with their specific recognition of single bone proteins

    No full text
    Bisphosphonates are nonbiodegradable pyrophosphate analogues that are increasingly used for inhibiting bone resorption in disorders characterized by excessive bone loss; they are in fact generally considered potent inhibitors of osteoclastic bone resorption both in vivo and in vitro but the mechanism by which these compounds exert their effect remains to be clarified. Data obtained on human systems in vitro are in particular lacking. The aim of this study was to assess the effect of etidronate (EHDP), one of the early compounds of bisphosphonates family, on osteoclast-matrix interactions and on bone resorption in a human in vitro system, using as an experimental model, osteoclast-like cells derived from giant cell tumors of bone (GCT). We reported that the presence of EHDP at the concentration ranging from 10-3 M to 10-7 M exerted a dose-dependent inhibition of the bone resorption activity with a maximal effect at 10-5 M. Because bisphosphonates owe the specificy of their actions to their ability of binding to bone surfaces, we performed adhesion assay using bone slices that had been pre-treated with solution of EHDP, at the established inhibitory concentration of hone resorption. Results showed that the morphology of cells plated onto bone slices pre-treated with the bisphosphonate was not significantly different from the control while the number of adherent cells was significantly reduced, by the treatment of about 50% vs control. Since osteoclast adhesion to the bone surface is mediated by the interaction with some adhesive proteins of extracellular bone matrix such as bone sialoprotein, osteopontin and fibronectin, furthermore the effect of EHDP on osteoclast adhesion onto specific extracellular matrix proteins, was also tested. In this case the presence of EHDP in the medium did not modify the percentage of cell adhesion compared to the control, indicating that the inhibitory effect of EHDP on cell adhesion onto hone slices, was probably not due to the interference with adhesion process of cells with specific hone matrix proteins. However we cannot exclude a possible effect on this process of EHDP that could be evident when all the components of the extracellular matrix ar present. In summary this work provides the first evidences of the inhibitory effect of EHDP on human osteoclast-like cells in vitro, confirming animal model data, possibly by a mechanism involving the adhesion process

    Breast cancer cell line MDA-231 stimulates osteoclastogenesis and bone resorption in human osteoclasts

    No full text
    Breast cancers commonly cause osteolytic metastases in bone, a process that is dependent upon osteoclast-mediated bone resorption, but the mechanism responsible for tumor-mediated osteoclast activation has not yet been clarified. In the present study we utilized a well-known human breast cancer cell line (MDA-231) in order to assess its capability to influence osteoclastogenesis in human bone marrow cultures and bone resorption in fully differentiated osteoclasts. We demonstrated that conditioned medium (CM) harvested from MDA-231 increased the formation of multinucleated TRAP-positive cells in bone marrow cultures. Bone resorption activity of fully differentiated human osteoclasts and of osteoclast-like cell lines, from giant cell tumors of bone (GCT), was highly increased by the presence of MDA-231 CM. Moreover, while MDA-231 by themselves did not produce IL-6 tumor cell, CM increased the secretion of IL-6 by primary human osteoclasts and GCT cell lines compared to untreated controls. These data suggest that MDA-231 produce osteoclastic activating factor(s) that increase both osteoclast formation in bone marrow culture and bone resorption activity by mature cells. Moreover, breast cancer cells stimulate IL-6 secretion by osteoclasts that is one of the factors known to supports osteoclastogenesis

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Full text link
    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

    Full text link
    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
    corecore