The Keio Journal of Medicine
Online ISSN : 1880-1293
Print ISSN : 0022-9717
ISSN-L : 0022-9717
Volume 60, Issue 4
Displaying 1-3 of 3 articles from this issue
REVIEWS
  • Takeshi Miyamoto
    2011 Volume 60 Issue 4 Pages 101-105
    Published: 2011
    Released on J-STAGE: December 25, 2011
    JOURNAL FREE ACCESS
    Osteoclasts are multinuclear giant cells derived from osteoclast/macrophage/dendritic cell common progenitor cells. The most characteristic feature of osteoclasts is multinucleation resulting from cell-cell fusion of mononuclear osteoclasts. Osteoclast cell-cell fusion is considered essential for re-organization of the cytoskeleton, such as the actin-ring and ruffled boarder to seal the resorbing area and to secret protons, respectively, to resorb bone; the fusion process is thus critical for osteoclast function. Various molecules, such as E-cadherin and macrophage fusion receptor (MFR), have been identified as regulators of osteoclast or macrophage cell-cell fusion. Laboratory production of osteoclasts used to be performed in a co-culture of osteoclast progenitors with osteoblastic cells, but recent advances in the identification of nuclear factor of kappa B ligand (RANKL) enabled the isolation of osteoclast-specific molecules involving osteoclast cell-cell fusion and differentiation regulators from purified osteoclast mRNA, since osteoclasts can be formed without osteoblasts. The essential cell-cell fusion regulator, dendritic cell-specific transmembrane protein (DC-STAMP), was isolated by a cDNA subtractive screen between mononuclear macrophages and RANKL-induced multinuclear osteoclasts. The cell-cell fusion of osteoclasts and foreign body giant cells (FBGCs) was completely abrogated in DC-STAMP-deficient mice in vivo and in vitro. Bone resorbing activity was significantly reduced but was still detected in DC-STAMP-deficient osteoclasts. DC-STAMP expression is positively regulated by two transcriptional factors: nuclear factor of activated T cells 1 (NFATc1) and c-Fos, both of which are essential for osteoclast differentiation. Furthermore, a novel osteoclastogenesis-regulating pathway involving two transcriptional repressors [B cell lymphoma 6 (Bcl6) and B lymphocyte-induced maturation protein 1 (Blimp1)] under RANKL stimulation has been discovered. The expression of osteoclastic genes such as DC-STAMP, NFATc1, and Cathepsin K, as well as osteoclast differentiation, was inhibited by Bcl6. Bcl6-deficient mice showed enhanced osteoclastogenesis and reduced bone mass, whereas osteoclast-specific Blimp1-conditional knockout mice showed elevated Bcl6 expression, osteoclastic gene expression, and osteoclast differentiation and increased bone mass. In this review, recent advances in our understanding of the regulators of osteoclast differentiation and cell-cell fusion are discussed.
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  • Tetsuro Setoyama, Hui Ling, Shoji Natsugoe, George A. Calin
    2011 Volume 60 Issue 4 Pages 106-113
    Published: 2011
    Released on J-STAGE: December 25, 2011
    JOURNAL FREE ACCESS
    Alterations in microRNA (miRNA) and other short or long non-coding RNA (ncRNA) are involved in the initiation, progression, and metastasis of human cancer. The main molecular alterations result from variations in gene expression, which are usually minor but have consequences for a vast number of target protein-coding genes. The causes of the widespread differential expression of ncRNAs in malignant cells compared with normal cells can be explained by the location of these genes in genomic regions associated with cancer, by epigenetic mechanisms, and by alterations in the processing machinery. Expression profiling of human tumors based on the expression of miRNAs and other short or long ncRNAs has identified signatures associated with diagnosis, staging, progression, prognosis, and response to treatment. In addition, profiling has been exploited to identify ncRNAs that may represent downstream targets of activated oncogenic pathways or that target protein-coding genes involved in cancer. Recent studies found that miRNAs and non-coding ultraconserved genes are the main candidates for the elusive class of cancer-predisposing genes and that other types of ncRNAs participate in the genetic puzzle that gives rise to the malignant phenotype. These discoveries could be exploited for the development of useful markers for diagnosis and prognosis in cancer, as well as for the development of new RNA-based cancer therapies.
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CASE REPORT
  • Takamichi Tohyama, Toshiyuki Fujiwara, Jun Matsumoto, Kaoru Honaga, Ju ...
    2011 Volume 60 Issue 4 Pages 114-118
    Published: 2011
    Released on J-STAGE: December 25, 2011
    JOURNAL FREE ACCESS
    Recently, surface electroencephalogram (EEG)-based brain-machine interfaces (BMI) have been used for people with disabilities. As a BMI signal source, event-related desynchronization of alpha-band EEG (8-13 Hz) during motor imagery (mu ERD), which is interpreted as desynchronized activities of the activated neurons, is commonly used. However, it is often difficult for patients with severe hemiparesis to produce mu ERD of sufficient strength to activate BMI. Therefore, whether it is possible to modulate mu ERD during motor imagery with anodal transcranial direct-current stimulation (tDCS) was assessed in a severe left hemiparetic stroke patient. EEG was recorded over the primary motor cortex (M1), and mu ERD during finger flexion imagery was measured before and after a 5-day course of tDCS applied to M1. The ERD recorded over the affected M1 increased significantly after tDCS intervention. Anodal tDCS may increase motor cortex excitability and potentiate ERD during motor imagery in patients with severe hemiparetic stroke.
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