osteoclasts

Summary

Summary: A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.

Top Publications

  1. ncbi Osteoclast differentiation and activation
    William J Boyle
    Protein Pathways, Inc, Woodland Hills, California 91367, USA
    Nature 423:337-42. 2003
  2. ncbi Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation
    D L Lacey
    Department of Pathology, Amgen, Inc, Thousand Oaks, California 91320 1789, USA
    Cell 93:165-76. 1998
  3. ncbi Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts
    Hiroshi Takayanagi
    Department of Immunology, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Japan
    Dev Cell 3:889-901. 2002
  4. ncbi The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation
    Kazuhisa Nakashima
    Department of Molecular Genetics and Program in Genes and Development, M D Anderson Cancer Center, University of Texas, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Cell 108:17-29. 2002
  5. ncbi Osteoprotegerin: a novel secreted protein involved in the regulation of bone density
    W S Simonet
    Department of Molecular Genetics, Amgen Inc, Thousand Oaks, California 91320, USA
    Cell 89:309-19. 1997
  6. pmc Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL
    H Yasuda
    Research Institute of Life Science, Snow Brand Milk Products Co, Ltd, 519 Ishibashi machi, Shimotsuga gun, Tochigi 329 0512, Japan
    Proc Natl Acad Sci U S A 95:3597-602. 1998
  7. ncbi Evidence for osteocyte regulation of bone homeostasis through RANKL expression
    Tomoki Nakashima
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo ku, Tokyo, Japan
    Nat Med 17:1231-4. 2011
  8. ncbi Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation
    Donald A Glass
    Department of Molecular and Human Genetics, Bone Disease Program of Texas, Houston, 77030, USA
    Dev Cell 8:751-64. 2005
  9. pmc IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis
    S Kotake
    The Institute of Rheumatology, Tokyo Women s Medical University, Tokyo 162 0054, Japan
    J Clin Invest 103:1345-52. 1999
  10. pmc Matrix-embedded cells control osteoclast formation
    Jinhu Xiong
    Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences UAMS, Little Rock, Arkansas, USA
    Nat Med 17:1235-41. 2011

Research Grants

  1. CELLULAR BASIS OF CRANIOFACIAL BONE DISORDERS
    Philip Osdoby; Fiscal Year: 2002
  2. Immune Regulation of Bone Homeostasis
    MERVYN NEALE WEITZMANN; Fiscal Year: 2012
  3. BONE MATRIX AND BONE RESORPTION
    Paul R Odgren; Fiscal Year: 2012
  4. Sirtuin/FOXO Signaling in the Regulation of Bone Mass
    Stavroula Kousteni; Fiscal Year: 2012
  5. Novel, Rapidly Translatable Technologies for Healing Long Bone Segmental Defects
    Christopher H Evans; Fiscal Year: 2010
  6. Anti-Inflammatory Glycosaminoglycan Ethers for Treatment of Periodontitis
    JUSTIN RODNEY SAVAGE; Fiscal Year: 2013
  7. Identification of Proteins Important for Male Osteoporosis
    Hong Wen Deng; Fiscal Year: 2013
  8. Runx Proteins and Sex Steroid Signaling in Bone
    Baruch Frenkel; Fiscal Year: 2009
  9. Inhibition of bone formation by Prx1
    Mark S Nanes; Fiscal Year: 2013
  10. Alcohol-Induced Bone Resorption: The Role of Oxidative Stress
    Martin J J Ronis; Fiscal Year: 2013

Detail Information

Publications374 found, 100 shown here

  1. ncbi Osteoclast differentiation and activation
    William J Boyle
    Protein Pathways, Inc, Woodland Hills, California 91367, USA
    Nature 423:337-42. 2003
    b>Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment...
  2. ncbi Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation
    D L Lacey
    Department of Pathology, Amgen, Inc, Thousand Oaks, California 91320 1789, USA
    Cell 93:165-76. 1998
    ..OPGL directly activates isolated mature osteoclasts in vitro, and short-term administration into normal adult mice results in osteoclast activation associated with ..
  3. ncbi Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts
    Hiroshi Takayanagi
    Department of Immunology, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Japan
    Dev Cell 3:889-901. 2002
    Signaling by RANKL is essential for terminal differentiation of monocytes/macrophages into osteoclasts. The TRAF6 and c-Fos signaling pathways both play important roles downstream of RANKL...
  4. ncbi The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation
    Kazuhisa Nakashima
    Department of Molecular Genetics and Program in Genes and Development, M D Anderson Cancer Center, University of Texas, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Cell 108:17-29. 2002
    ..In endochondral skeletal elements of Osx null mice, mesenchymal cells, together with osteoclasts and blood vessels, invade the mineralized cartilage matrix...
  5. ncbi Osteoprotegerin: a novel secreted protein involved in the regulation of bone density
    W S Simonet
    Department of Molecular Genetics, Amgen Inc, Thousand Oaks, California 91320, USA
    Cell 89:309-19. 1997
    ..These data show that OPG can act as a soluble factor in the regulation of bone mass and imply a utility for OPG in the treatment of osteoporosis associated with increased osteoclast activity...
  6. pmc Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL
    H Yasuda
    Research Institute of Life Science, Snow Brand Milk Products Co, Ltd, 519 Ishibashi machi, Shimotsuga gun, Tochigi 329 0512, Japan
    Proc Natl Acad Sci U S A 95:3597-602. 1998
    b>Osteoclasts, the multinucleated cells that resorb bone, develop from hematopoietic cells of monocyte/macrophage lineage...
  7. ncbi Evidence for osteocyte regulation of bone homeostasis through RANKL expression
    Tomoki Nakashima
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo ku, Tokyo, Japan
    Nat Med 17:1231-4. 2011
    ..been postulated to orchestrate bone homeostasis by regulating both bone-forming osteoblasts and bone-resorbing osteoclasts. We find here that purified osteocytes express a much higher amount of receptor activator of nuclear factor-κB ..
  8. ncbi Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation
    Donald A Glass
    Department of Molecular and Human Genetics, Bone Disease Program of Texas, Houston, 77030, USA
    Dev Cell 8:751-64. 2005
    ....
  9. pmc IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis
    S Kotake
    The Institute of Rheumatology, Tokyo Women s Medical University, Tokyo 162 0054, Japan
    J Clin Invest 103:1345-52. 1999
    ..with recombinant human IL-17 induced the formation of multinucleated cells, which satisfied major criteria of osteoclasts, including tartrate-resistant acid phosphatase activity, calcitonin receptors, and pit formation on dentine ..
  10. pmc Matrix-embedded cells control osteoclast formation
    Jinhu Xiong
    Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences UAMS, Little Rock, Arkansas, USA
    Nat Med 17:1235-41. 2011
    b>Osteoclasts resorb the mineralized matrices formed by chondrocytes or osteoblasts...
  11. ncbi Mechanisms of bone metastasis
    G David Roodman
    Department of Medicine, Division of Hematology Oncology, University of Pittsburgh, School of Medicine Hematology, The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
    N Engl J Med 350:1655-64. 2004
  12. ncbi The molecular understanding of osteoclast differentiation
    Masataka Asagiri
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Tokyo 113 8549, Japan
    Bone 40:251-64. 2007
    b>Osteoclasts are multinucleated cells of monocyte/macrophage origin that degrade bone matrix...
  13. pmc Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand
    H Hsu
    Department of Cell Biology, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
    Proc Natl Acad Sci U S A 96:3540-5. 1999
    ..The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo...
  14. ncbi Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families
    T Suda
    Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan
    Endocr Rev 20:345-57. 1999
    ..RANKL is also involved in the survival and fusion of pOCs and activation of mature osteoclasts. OPG, which has also been called OCIF or TR1, is a soluble receptor for RANKL and acts as a decoy receptor in ..
  15. ncbi RANKL-RANK signaling in osteoclastogenesis and bone disease
    Teiji Wada
    Institute of Molecular Biotechnology of the Austrian Academy of Sciences IMBA, Dr Bohrgasse 3, A 1030 Vienna, Austria
    Trends Mol Med 12:17-25. 2006
    ..Designing novel drugs that target RANKL-RANK and their signaling pathways in osteoclasts could potentially revolutionize the treatment of many diseases associated with bone loss such as arthritis, ..
  16. ncbi Therapeutic approaches to bone diseases
    G A Rodan
    Merck Research Laboratories, West Point, PA 19486, USA St Vincent s Institute of Medical Research, Melbourne 3065, Australia
    Science 289:1508-14. 2000
    The strength and integrity of our bones depends on maintaining a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts...
  17. ncbi OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis
    Y Y Kong
    Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada
    Nature 397:315-23. 1999
    ..Mice with a disrupted opgl gene show severe osteopetrosis and a defect in tooth eruption, and completely lack osteoclasts as a result of an inability of osteoblasts to support osteoclastogenesis...
  18. ncbi The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor
    B R Wong
    Laboratory of Immunology, The Rockefeller University, New York, New York 10021, USA
    J Biol Chem 273:28355-9. 1998
    ..T-cells, bone marrow stromal cells, and osteoblasts, regulates the function of dendritic cells (DC) and osteoclasts. The TRANCE receptor (TRANCE-R), recently identified as receptor activator of NF-kappabeta (RANK), activates NF-..
  19. ncbi Transforming growth factor-beta1 to the bone
    Katrien Janssens
    Department of Medical Genetics, University of Antwerp, Campus Drie Eiken, 2610 Antwerp, Belgium
    Endocr Rev 26:743-74. 2005
    ..This review provides an overall picture of the bone-specific actions of TGF-beta1 and reconciles experimental discrepancies that have been reported for this multifunctional cytokine...
  20. ncbi c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling
    A E Grigoriadis
    Research Institute of Molecular Pathology IMP, Vienna, Austria
    Science 266:443-8. 1994
    ..Fos mutant mice were found to have a block in the differentiation of bone-resorbing osteoclasts that was intrinsic to hematopoietic cells...
  21. ncbi Essential role of beta-catenin in postnatal bone acquisition
    Sheri L Holmen
    Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
    J Biol Chem 280:21162-8. 2005
    ..Loss of beta-catenin produced severe osteopenia with striking increases in osteoclasts, whereas constitutive activation of beta-catenin in the conditional Apc mutants resulted in dramatically ..
  22. pmc Receptor activator of nuclear factor κB ligand (RANKL) protein expression by B lymphocytes contributes to ovariectomy-induced bone loss
    Melda Onal
    Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    J Biol Chem 287:29851-60. 2012
    ..These results demonstrate that lymphocyte RANKL is not involved in basal bone remodeling, but B cell RANKL does contribute to the increase in osteoclasts and cancellous bone loss that occurs after loss of estrogen.
  23. pmc Role of NF-κB in the skeleton
    Deborah Veis Novack
    Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
    Cell Res 21:169-82. 2011
    ..NF-κB controls the differentiation or activity of the major skeletal cell types - osteoclasts, osteoblasts, osteocytes and chondrocytes...
  24. ncbi Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Nat Rev Immunol 7:292-304. 2007
    ..Although osteoimmunology started with the study of the immune regulation of osteoclasts, its scope has been extended to encompass a wide range of molecular and cellular interactions, including those ..
  25. ncbi Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL
    J G Emery
    Department of Molecular Biology, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 273:14363-7. 1998
    ..OPG inhibits TRAIL-induced apoptosis of Jurkat cells. Conversely, TRAIL blocks the anti-osteoclastogenic activity of OPG. These data suggest potential cross-regulatory mechanisms by OPG and TRAIL...
  26. pmc Autoamplification of NFATc1 expression determines its essential role in bone homeostasis
    Masataka Asagiri
    Department of Cell Signaling, Tokyo Medical and Dental University, Japan
    J Exp Med 202:1261-9. 2005
    ..redundant in the immune system, but it was suggested that NFATc1 is required exclusively for differentiation of osteoclasts in the skeletal system...
  27. pmc Functions of RANKL/RANK/OPG in bone modeling and remodeling
    Brendan F Boyce
    Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, NY 14642, USA
    Arch Biochem Biophys 473:139-46. 2008
    ..Thus, the relative concentration of RANKL and OPG in bone is a major determinant of bone mass and strength. Here, we review our current understanding of the role of the RANKL/RANK/OPG system in bone modeling and remodeling...
  28. pmc RANK is essential for osteoclast and lymph node development
    W C Dougall
    Immunex Corporation, Seattle, Washington 98101 USA
    Genes Dev 13:2412-24. 1999
    ..myeloid precursors but provided a necessary and specific signal for the differentiation of myeloid-derived osteoclasts. RANK(-/-) mice also exhibited a marked deficiency of B cells in the spleen...
  29. ncbi An overview of the regulation of bone remodelling at the cellular level
    Jasreen Kular
    School of Pathology and Laboratory Medicine, The University of Western Australia, Western Australia, Australia
    Clin Biochem 45:863-73. 2012
    ..To review the current literature on the regulation of bone remodelling at the cellular level...
  30. ncbi Stimulation of bone formation in vitro and in rodents by statins
    G Mundy
    OsteoScreen, 2040 Babcock Road, San Antonio, TX 78229, USA
    Science 286:1946-9. 1999
    ..Thus, in appropriate doses, statins may have therapeutic applications for the treatment of osteoporosis...
  31. ncbi Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis
    Takako Koga
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Nature 428:758-63. 2004
    ..Receptor activator of NF-kappaB ligand (RANKL) regulates the differentiation of bone-resorbing cells, osteoclasts, in the presence of macrophage-colony stimulating factor (M-CSF)...
  32. ncbi Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro
    H Yasuda
    Research Institute of Life Science, Snow Brand Milk Products Co, Ltd, Tochigi, Japan
    Endocrinology 139:1329-37. 1998
    The morphogenesis and remodeling of bone depends on the integrated activity of osteoblasts that form bone and osteoclasts that resorb bone...
  33. ncbi A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation
    Na Kyung Lee
    Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul, 120 750, Korea
    Blood 106:852-9. 2005
    ..ligand (RANKL) is essential for differentiation of bone marrow monocyte-macrophage lineage (BMM) cells into osteoclasts. Here, we show RANKL stimulation of BMM cells transiently increased the intracellular level of reactive oxygen ..
  34. ncbi Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro
    Edith Bonnelye
    Laboratoire de Génomique Fonctionelle de Lyon, Université de Lyon UMR5242, CNRS INRA ENS Université Lyon1 IFR 128 Biosciences Lyon Gerland, 46, Allee d Italie, 69007 Lyon, France
    Bone 42:129-38. 2008
    ..the dual mode of action of strontium ranelate in bone was tested in vitro, on primary murine osteoblasts and osteoclasts derived from calvaria and spleen cells, respectively...
  35. pmc The architecture of the adhesive apparatus of cultured osteoclasts: from podosome formation to sealing zone assembly
    Chen Luxenburg
    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    PLoS ONE 2:e179. 2007
    b>Osteoclasts are bone-degrading cells, which play a central role in physiological bone remodeling. Unbalanced osteoclast activity is largely responsible for pathological conditions such as osteoporosis...
  36. pmc Cellular and molecular mechanisms of bone remodeling
    Liza J Raggatt
    Faculty of Health Sciences, The University of Queensland Centre for Clinical Research, Royal Brisbane Hospital, Herston 4029, Australia
    J Biol Chem 285:25103-8. 2010
    ..In addition to the traditional bone cells (osteoclasts, osteoblasts, and osteocytes) that are necessary for bone remodeling, several immune cells have also been ..
  37. pmc Normal bone anatomy and physiology
    Bart Clarke
    Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, W18 A, 200 1st Street SW, Rochester, MN 55905, USA
    Clin J Am Soc Nephrol 3:S131-9. 2008
    ..This information lays the groundwork for understanding the utility and clinical applications of iliac crest bone biopsy...
  38. ncbi Reactive oxygen species stimulates receptor activator of NF-kappaB ligand expression in osteoblast
    Xiao Chun Bai
    Department of Cell Biology, Southern Medical University, Guangzhou 510515, China
    J Biol Chem 280:17497-506. 2005
    ..These results demonstrate that ROS stimulates RANKL expression via ERKs and PKA-CREB pathway in mouse osteoblasts and via ERKs and HSF2 in human MG63 cells...
  39. ncbi Filamin A regulates monocyte migration through Rho small GTPases during osteoclastogenesis
    Roland Leung
    CIHR Group in Matrix Dynamics, University of Toronto, Toronto, Ontario, Canada
    J Bone Miner Res 25:1077-91. 2010
    ..the tibiae and femora of wild type (WT) and Flna-null mice were cultured for 6 days with M-CSF and RANKL, and osteoclasts were identified by tartrate-resistant acid phosphatase (TRACP) staining...
  40. ncbi Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization
    Mei Zhang
    Department of Medicine, University of Cincinnati, Ohio 45267, USA
    J Biol Chem 277:44005-12. 2002
    ..This action is likely to be particularly important during the pubertal growth spurt when rapid bone formation and consolidation are required...
  41. ncbi Osteopetrosis in mice lacking haematopoietic transcription factor PU.1
    M M Tondravi
    Department of Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Nature 386:81-4. 1997
    b>Osteoclasts are multinucleated cells and the principal resorptive cells of bone. Although osteoclasts are of myeloid origin, the role of haematopoietic transcription factors in osteoclastogenesis has not been explored...
  42. pmc Bone damage in rheumatoid arthritis: mechanistic insights and approaches to prevention
    Sougata Karmakar
    Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, UMass Memorial Medical Center, Lazare Research Building, Suite 223, 364 Plantation Street, Worcester, MA 01605, USA
    Rheum Dis Clin North Am 36:385-404. 2010
    ..In this review, the authors discuss the current understanding of pathogenic mechanisms of bone erosion in RA and examine current therapeutic approaches to prevent this damage...
  43. ncbi The osteoclast and its unique cytoskeleton
    Steven L Teitelbaum
    Departments of Pathology and Immunology, and Medicine, Washington University School of Medicine, St Louis, Missouri, USA
    Ann N Y Acad Sci 1240:14-7. 2011
    ..Absence of any component of this signaling pathway compromises osteoclast cytoskeletal organization and abridges bone resorption...
  44. pmc Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis
    Christopher T Ritchlin
    Allergy, Immunology and Rheumatology Unit, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Clin Invest 111:821-31. 2003
    ..Moreover, PsA PBMCs readily formed osteoclasts in vitro without exogenous receptor activator of NF-kappaB ligand (RANKL) or MCSF...
  45. ncbi Regulatory mechanisms of osteoblast and osteoclast differentiation
    T Katagiri
    Department of Biochemistry, School of Dentistry, Showa University, Japan
    Oral Dis 8:147-59. 2002
    ..Osteoblasts and osteoclasts are specialized cells responsible for bone formation and resorption, respectively...
  46. pmc Directed differentiation of hematopoietic precursors and functional osteoclasts from human ES and iPS cells
    Agamemnon E Grigoriadis
    Department of Craniofacial Development and Orthodontics, Guy s Hospital, King s College London, London, UK
    Blood 115:2769-76. 2010
    ..Here, we report the stepwise generation of bone-resorbing osteoclasts from human embryonic and induced pluripotent stem cells...
  47. ncbi v-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation
    Seoung Hoon Lee
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Nat Med 12:1403-9. 2006
    Matrix-producing osteoblasts and bone-resorbing osteoclasts maintain bone homeostasis. Osteoclasts are multinucleated, giant cells of hematopoietic origin formed by the fusion of mononuclear pre-osteoclasts derived from myeloid cells...
  48. ncbi Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis
    S C Manolagas
    Division of Endocrinology and Metabolism, University of Arkansas for Medical Sciences, Little Rock 72205, USA
    Endocr Rev 21:115-37. 2000
    The adult skeleton regenerates by temporary cellular structures that comprise teams of juxtaposed osteoclasts and osteoblasts and replace periodically old bone with new...
  49. ncbi Involvement of p38 mitogen-activated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of NF-kappa B ligand (RANKL)
    M Matsumoto
    Laboratories of Cellular Biochemistry and Antibiotics, RIKEN The Institute of Physical and Chemical Research, 2 1 Hirosawa, Wako, Saitama, 351 0198 Japan
    J Biol Chem 275:31155-61. 2000
    ..These results indicate that activation of the p38 MAP kinase pathway plays an important role in RANKL-induced osteoclast differentiation of precursor bone marrow cells...
  50. ncbi Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases
    Lorenz C Hofbauer
    Department of Gastroenterology, Philipps University, Marburg, Germany
    JAMA 292:490-5. 2004
    Bone resorption by osteoclasts is coupled with bone formation by osteoblasts, and this balanced process continuously remodels and adapts the skeleton...
  51. ncbi Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy
    R G G Russell
    Nuffield Department of Orthopaedic Surgery, Oxford University Institute of Musculoskeletal Sciences The Botnar Research Centre, Nuffield Orthopaedic Centre, Headington, Oxford OX3 7LD, UK
    Osteoporos Int 19:733-59. 2008
    ..There is new knowledge about how they work. The differences that exist among individual BPs in terms of mineral binding and biochemical actions may explain differences in their clinical behavior and effectiveness...
  52. ncbi Bone remodeling during fracture repair: The cellular picture
    Aaron Schindeler
    Department of Orthopaedic Research and Biotechnology, The Children s Hospital at Westmead, Sydney, Australia
    Semin Cell Dev Biol 19:459-66. 2008
    ..In normal bone development, bone remodeling conventionally refers to the removal of calcified bone tissue by osteoclasts. However, in the context of bone repair there are two phases of tissue catabolism: the removal of the initial ..
  53. ncbi Suppression of bone formation by osteoclastic expression of semaphorin 4D
    Takako Negishi-Koga
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
    Nat Med 17:1473-80. 2011
    ..It is thus becoming increasingly necessary to identify the factors that regulate bone formation. We found that osteoclasts express semaphorin 4D (Sema4D), previously shown to be an axon guidance molecule, which potently inhibits bone ..
  54. ncbi Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU.1
    Masahito Matsumoto
    Department of Molecular Biology, Saitama Medical School, Saitama, Japan
    J Biol Chem 279:45969-79. 2004
    ..RANKL-induced NFATc1 forms a complex with PU.1 in nuclei of osteoclasts following the nuclear accumulation of NFATc1 phosphorylated by the activated p38 MAP kinase...
  55. pmc IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation
    Yuhao Gao
    Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, Georgia 30322, USA
    J Clin Invest 117:122-32. 2007
    ..Inhibition of IFN-gamma signaling may thus represent a novel strategy to simultaneously reduce inflammation and bone loss in common forms of osteoporosis...
  56. ncbi Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos
    Koichi Matsuo
    Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo 160 8582, Japan
    J Biol Chem 279:26475-80. 2004
    b>Osteoclasts are specialized macrophages that resorb bone. Mice lacking the AP-1 component c-Fos are osteopetrotic because of a lack of osteoclast differentiation and show an increased number of macrophages...
  57. pmc Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells
    Suwen Wei
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    J Leukoc Biol 88:495-505. 2010
    ..CSF-1R tyrosine phosphorylation, and signaling and synergized with other cytokines to generate macrophages and osteoclasts from cultured progenitors...
  58. ncbi Podosome and sealing zone: specificity of the osteoclast model
    Pierre Jurdic
    Laboratoire de Biologie Moléculaire et Cellulaire UMR 5161 CNRS ENS, IFR 128 BioSciences, Ecole Normale Superieure de Lyon, 46 allee d Italie, F 69007 Lyon, France
    Eur J Cell Biol 85:195-202. 2006
    The bone resorption function of osteoclasts is dependent on the integrity of the actin cytoskeleton...
  59. pmc DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells
    Mitsuru Yagi
    Department of Cell Differentiation, The Sakaguchi Laboratory, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    J Exp Med 202:345-51. 2005
    b>Osteoclasts are bone-resorbing cells that play a pivotal role in bone remodeling. Osteoclasts form large multinuclear giant cells by fusion of mononuclear osteoclasts. How cell fusion is mediated, however, is unclear...
  60. ncbi Dissociation of the pro-apoptotic effects of bisphosphonates on osteoclasts from their anti-apoptotic effects on osteoblasts/osteocytes with novel analogs
    Lilian I Plotkin
    Division of Endocrinology and Metabolism, the Center for Osteoporosis and Metabolic Bone Diseases, The Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, 4301 West Markham, Mail Slot 587, Little Rock, AR 72205, USA
    Bone 39:443-52. 2006
    ..On the other hand, only 10 analogs induced apoptosis of RAW-264.7-cell-derived osteoclasts. Each of the 6 bisphosphonates that lack pro-apoptotic activity in osteoclasts but retain anti-apoptotic ..
  61. pmc CD8+ T cells regulate bone tumor burden independent of osteoclast resorption
    Kaihua Zhang
    Department of Orthopedics, Washington University School of Medicine, St Louis, MO 63110, USA
    Cancer Res 71:4799-808. 2011
    ..Our findings show the important contribution of CD8(+) T cells in the regulation of bone metastases regardless of OC status, thus including T cells as critical regulators of tumor growth in bone...
  62. ncbi Mangiferin attenuates osteoclastogenesis, bone resorption, and RANKL-induced activation of NF-κB and ERK
    Estabelle Ang
    School of Surgery, The University of Western Australia, Nedlands, Western Australia 6009, Australia
    J Cell Biochem 112:89-97. 2011
    ..drives the activation of downstream signaling pathways; which ultimately induce the formation and activation of osteoclasts. In this study, we showed that a natural immunomodulator, mangiferin, inhibits osteoclast formation and bone ..
  63. ncbi Lysosomal pathology and osteopetrosis upon loss of H+-driven lysosomal Cl- accumulation
    Stefanie Weinert
    Leibniz Institut fur Molekulare Pharmakologie FMP, 13125 Berlin, Germany
    Science 328:1401-3. 2010
    ..This conductance was even deleterious in Clcn7(+/unc) mice. Clcn7(-/-) and Clcn7(unc/unc) mice accumulated less Cl- in lysosomes than did wild-type mice. Thus, lowered lysosomal chloride may underlie their common phenotypes...
  64. ncbi Osteoclast nuclei of myeloma patients show chromosome translocations specific for the myeloma cell clone: a new type of cancer-host partnership?
    T L Andersen
    Department of Clinical Cell Biology KCB, Southern Denmark University, CeSFUVA, Vejle Hospital, 7100 Vejle, Denmark
    J Pathol 211:10-7. 2007
    ..It is widely accepted that this destruction is not caused by the malignant cells themselves, but by osteoclasts, multinucleated cells of monocytic origin that are considered to be the only cells able to degrade bone...
  65. pmc M-CSF potently augments RANKL-induced resorption activation in mature human osteoclasts
    Jason M Hodge
    The Department of Clinical and Biomedical Sciences, Barwon Health, The University of Melbourne, Geelong, Victoria, Australia
    PLoS ONE 6:e21462. 2011
    ..Our results reveal a previously unidentified role of M-CSF as a potent stimulator of mature OC resorbing activity, possibly mediated via ERK upstream of c-fos...
  66. ncbi New insights into osteoclastogenic signaling mechanisms
    Tomoki Nakashima
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Trends Endocrinol Metab 23:582-90. 2012
    ..This process is the fundamental basis for the maintenance of normal bone mass and architecture. Osteoclasts play a crucial role in both physiological and pathological bone resorption, and receptor activator of nuclear ..
  67. ncbi RANK signaling is not required for TNFalpha-mediated increase in CD11(hi) osteoclast precursors but is essential for mature osteoclast formation in TNFalpha-mediated inflammatory arthritis
    Ping Li
    Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Bone Miner Res 19:207-13. 2004
    ..RANK signaling is not required for the TNFalpha-stimulated increase in CD11b(hi) osteoclast precursors but is essential for mature osteoclast formation...
  68. pmc RGS10-null mutation impairs osteoclast differentiation resulting from the loss of [Ca2+]i oscillation regulation
    Shuying Yang
    Department of Cytokine Biology, The Forsyth Institute, Boston, Massachusetts 02115, USA
    Genes Dev 21:1803-16. 2007
    ..signaling proteins and found regulator of G-protein signaling 10 (RGS10) is predominantly expressed in osteoclasts. We generated RGS10-deficient (RGS10-/-) mice that exhibited severe osteopetrosis and impaired osteoclast ..
  69. ncbi IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology
    Steeve Kwan Tat
    Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculte de Medecine, 1 rue Gaston Veil, BP 53508, 44035 Nantes 1, France
    Cytokine Growth Factor Rev 15:49-60. 2004
    All osteogenic cells (osteoclasts, osteoblasts) contribute individually to bone remodeling. Their cellular interactions control their cellular activities and the bone remodeling intensity...
  70. pmc Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis
    Nacksung Kim
    Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, Korea
    J Exp Med 202:589-95. 2005
    b>Osteoclasts are derived from myeloid lineage cells, and their differentiation is supported by various osteotropic factors, including the tumor necrosis factor (TNF) family member TNF-related activation-induced cytokine (TRANCE)...
  71. pmc IL-1 mediates TNF-induced osteoclastogenesis
    Shi Wei
    Department of Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Clin Invest 115:282-90. 2005
    ..Thus, IL-1 mediates the osteoclastogenic effect of TNF by enhancing stromal cell expression of RANKL and directly stimulating differentiation of osteoclast precursors...
  72. ncbi Osteoimmunology and the effects of the immune system on bone
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan
    Nat Rev Rheumatol 5:667-76. 2009
    ..The interaction between T cells and osteoclasts is a critical issue in the field of osteoimmunology...
  73. ncbi Localization of RANKL (receptor activator of NF kappa B ligand) mRNA and protein in skeletal and extraskeletal tissues
    V Kartsogiannis
    Department of Medicine, The University of Melbourne and St Vincent s Institute of Medical Research, St Vincent s Hospital, Fitzroy, Victoria, Australia
    Bone 25:525-34. 1999
    ..Expression of RANKL mRNA and protein in osteoclasts was variable with those within resorption lacunae showing the strongest signal/staining...
  74. ncbi Osteoclast-osteoblast communication
    Koichi Matsuo
    Department of Microbiology and Immunology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku ku, 160 8582 Tokyo, Japan
    Arch Biochem Biophys 473:201-9. 2008
    ..c-Fms, RANK and costimulatory molecules, such as osteoclast-associated receptor (OSCAR), and differentiate into osteoclasts following cell-cell contact with osteoblasts, which express ligands...
  75. ncbi Large scale gene expression analysis of osteoclastogenesis in vitro and elucidation of NFAT2 as a key regulator
    Norihiro Ishida
    Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630 0101, Japan
    J Biol Chem 277:41147-56. 2002
    ..identified as genes whose enhanced expressions were fairly correlated with an efficient induction of matured osteoclasts. Moreover, cyclosporin A significantly suppressed the multinucleated cell formation accompanying the reduction ..
  76. pmc B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease
    Toshihisa Kawai
    Department of Immunology, The Forsyth Institute, 140 The Fenway, Boston, MA 02115, USA
    Am J Pathol 169:987-98. 2006
    ..These results suggest that activated T and B cells can be the cellular source of RANKL for bone resorption in periodontal diseased gingival tissue...
  77. ncbi Denosumab and bisphosphonates: different mechanisms of action and effects
    Roland Baron
    Department of Medicine, Harvard Medical School, Endocrine Unit, Massachusetts General Hospital, Boston, MA 02115, USA
    Bone 48:677-92. 2011
    ..and/or focal osteolysis as in rheumatoid arthritis or periodontal disease, most approaches target the osteoclasts, the cells that resorb bone. Bisphosphonates are currently the most widely used antiresorptive therapies...
  78. pmc Cellular mechanisms of bone remodeling
    Erik Fink Eriksen
    Department of Clinical Endocrinology, Oslo University Hospital, Aker, Trondheimsveien 235, 0514 Oslo, Norway
    Rev Endocr Metab Disord 11:219-27. 2010
    ..The dominant pathway regulating osteoclast recruitment is the RANKL/OPG system, while many different factors (RUNX, Osterix) are involved in osteoblast differentiation. Both pathways are modulated by calcitropic hormones...
  79. ncbi Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors
    Niklas R Jørgensen
    Osteoporosis Research Clinic, Dept 545, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, Hvidovre DK 2650, Denmark
    J Biol Chem 277:7574-80. 2002
    Signaling between osteoblasts and osteoclasts is important in bone homeostasis...
  80. ncbi Blockade of the pore-forming P2X7 receptor inhibits formation of multinucleated human osteoclasts in vitro
    A Gartland
    Human Bone Cell Research Group, Department Human Anatomy and Cell Biology, The University of Liverpool, Liverpool, L69 3GE, UK Alison Gartland umassmed edu
    Calcif Tissue Int 73:361-9. 2003
    b>Osteoclasts are large, multinucleated, terminally differentiated cells formed by the fusion of mononuclear hemopoietic precursors...
  81. ncbi Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis
    Chen Zhao
    Department of Microbiology and Immunology, School of Medicine, Keio University, Shinjuku ku, Tokyo, 160 8582, Japan
    Cell Metab 4:111-21. 2006
    Bone homeostasis requires a delicate balance between the activities of bone-resorbing osteoclasts and bone-forming osteoblasts...
  82. ncbi Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival
    L Lum
    Tri Institutional Cornell Rockefeller University Memorial Sloan Kettering Cancer Center, Training Program, New York, New York 10021, USA
    J Biol Chem 274:13613-8. 1999
    ..We propose that the TRANCE ectodomain is released from cells by TACE or a related metalloprotease-disintegrin, and that this release is an important component of the function of TRANCE in bone and immune homeostasis...
  83. pmc Gelsolin deficiency blocks podosome assembly and produces increased bone mass and strength
    M Chellaiah
    Renal Division, Department of Medicine, Barnes Jewish Hospital, Washington University, St Louis, Missouri 63110, USA
    J Cell Biol 148:665-78. 2000
    b>Osteoclasts are unique cells that utilize podosomes instead of focal adhesions for matrix attachment and cytoskeletal remodeling during motility...
  84. ncbi Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL
    Paul J Kostenuik
    Metabolic Disorders Research, Amgen, Thousand Oaks, California 91320, USA
    J Bone Miner Res 24:182-95. 2009
    ..These huRANKL mice have potential utility for characterizing the activity of denosumab in a variety of murine bone disease models...
  85. pmc The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts
    T L Burgess
    Department of Mammalian Cell Molecular Biology, Amgen Inc, Thousand Oaks, California 91320 1789, USA
    J Cell Biol 145:527-38. 1999
    ..Elliott, A. Colombero, G. Elliott, S. Scully, et al. 1998. Cell. 93: 165-176), but their effects on mature osteoclasts are not well understood...
  86. ncbi Regulatory mechanism of NFATc1 in RANKL-induced osteoclast activation
    Insun Song
    National Research Laboratory for Regulation of Bone Metabolism and Disease, Medical Research Center for Gene Regulation, Brain Korea 21, Chonnam National University Medical School, 5 Hak dong, Dong Ku, Gwangju 501 746, Republic of Korea
    FEBS Lett 583:2435-40. 2009
    ..attenuates RANKL-induced bone resorption and overexpression of a constitutively active form of NFATc1 in osteoclasts induces formation of actin rings and resorption pits on dentin slices...
  87. ncbi AMP kinase acts as a negative regulator of RANKL in the differentiation of osteoclasts
    Young Sun Lee
    Asan Institute for Life Sciences, Seoul 138 736, Republic of Korea
    Bone 47:926-37. 2010
    AMP-activated protein kinase (AMPK) has been reported to stimulate differentiation and proliferation of osteoblasts, but the role of AMPK in the physiology of osteoclasts has not been investigated.
  88. ncbi Estrogens maintain bone mass by regulating expression of genes controlling function and life span in mature osteoclasts
    Yuuki Imai
    Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
    Ann N Y Acad Sci 1173:E31-9. 2009
    ..in regulation of bone mass and strength by controlling activity of bone-forming osteoblasts and bone-resorbing osteoclasts. Cellular effects of estrogens are mediated predominantly by the action of estrogen receptor alpha (ERalpha)...
  89. ncbi Bone remodeling in post-menopausal osteoporosis
    U H Lerner
    Department of Oral Cell Biology, Umea University, Umea SE 901 87, Sweden
    J Dent Res 85:584-95. 2006
    ..mass in the skeleton is dependent on the coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts in discrete bone multi-cellular units...
  90. pmc Macrophage fusion: the making of osteoclasts and giant cells
    AGNES VIGNERY
    Yale University School of Medicine, New Haven, CT 06510, USA
    J Exp Med 202:337-40. 2005
    ..Fusion is required for the formation of multinucleated osteoclasts and giant cells, although the mechanisms that govern these processes are poorly understood...
  91. ncbi P2 receptor expression, signaling and function in osteoclasts
    Juan P Reyes
    Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada
    Front Biosci (Schol Ed) 3:1101-18. 2011
    Skeletal development and bone remodeling depend on the coordinated activity of osteoblasts and osteoclasts, which are responsible for bone formation and resorption, respectively...
  92. pmc Osteoimmunology at the nexus of arthritis, osteoporosis, cancer, and infection
    Dallas Jones
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    J Clin Invest 121:2534-42. 2011
    ....
  93. pmc Regulation of sealing ring formation by L-plastin and cortactin in osteoclasts
    Tao Ma
    Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, Maryland 21201, USA
    J Biol Chem 285:29911-24. 2010
    ..demonstrated a significant increase in cortactin and a corresponding decrease in L-plastin protein levels in osteoclasts subjected to bone resorption for 18 h in the presence of RANKL, M-CSF, and native bone particles...
  94. ncbi Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion
    Masahiro Abe
    Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3 18 15 Kuramoto cho, Tokushima, 770 8503, Japan
    Blood 104:2484-91. 2004
    ..by enhancing osteoclastic bone resorption in its vicinity, suggesting a close interaction between MM cells and osteoclasts (OCs)...
  95. pmc Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(-/-) mice
    Hava Gil-Henn
    Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06511, USA
    J Cell Biol 178:1053-64. 2007
    The protein tyrosine kinase Pyk2 is highly expressed in osteoclasts, where it is primarily localized in podosomes. Deletion of Pyk2 in mice leads to mild osteopetrosis due to impairment in osteoclast function...
  96. ncbi Macrophage inflammatory protein-1alpha is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor kappaB ligand
    J H Han
    Department of Medicine/Hematology, University of Texas Health Science Center, San Antonio, TX 78284, USA
    Blood 97:3349-53. 2001
    ..Blood. 2001;97:3349-3353)..
  97. ncbi The role of NFAT in osteoclast formation
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Ann N Y Acad Sci 1116:227-37. 2007
    b>Osteoclasts are cells of monocyte-macrophage origin that degrade bone matrix...
  98. ncbi Expression of Nox4 in osteoclasts
    Su Yang
    Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA
    J Cell Biochem 92:238-48. 2004
    ..In this study, we demonstrated that Nox4 is expressed at a higher level in osteoclasts than that in precursor cells...
  99. pmc Estrogen blocks M-CSF gene expression and osteoclast formation by regulating phosphorylation of Egr-1 and its interaction with Sp-1
    S Srivastava
    Division of Bone and Mineral Diseases, Washington University School of Medicine, and Barnes Jewish Hospital, St Louis, Missouri 63110, USA
    J Clin Invest 102:1850-9. 1998
    ..Thus, by downregulating formation of a novel Egr-1/Sp-1 complex in stromal cells, estrogen deficiency results in enhanced levels of free Sp-1 and increased M-CSF gene expression and osteoclast formation...
  100. ncbi Decoy receptor 3 (DcR3) induces osteoclast formation from monocyte/macrophage lineage precursor cells
    C R Yang
    Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan
    Cell Death Differ 11:S97-107. 2004
    ..7 macrophages, and bone marrow cells. DcR3-differentiated cells exhibit characteristics unique for osteoclasts, including polynuclear giant morphology, bone resorption, TRAP, CD51/61, and MMP-9 expression...
  101. ncbi NF-kB signaling blockade abolishes implant particle-induced osteoclastogenesis
    John C Clohisy
    Department of Orthopaedic Surgery, Barnes Jewish Hospital at Washington University School of Medicine, One Barnes Jewish Hospital Plaza, Suite 11300, West Pavillion, St Louis, MO 63110, USA
    J Orthop Res 22:13-20. 2004
    ..Again, this inhibitor efficiently blocked particle-induced osteoclastogenesis. Thus, we have shown that pharmaceutical and molecular blockade of NF-kB activation inhibits PMMA particle-directed osteoclastogenesis in vitro...

Research Grants74

  1. CELLULAR BASIS OF CRANIOFACIAL BONE DISORDERS
    Philip Osdoby; Fiscal Year: 2002
    ..Information is just beginning to emerge that osteoclasts themselves synthesize and release factors that may influence bone remodeling...
  2. Immune Regulation of Bone Homeostasis
    MERVYN NEALE WEITZMANN; Fiscal Year: 2012
    ..The bone destruction that drives osteoporosis is mediated by osteoclasts (OCs), bone resorbing cells that form under the influence of the key osteoclastogenic cytokine Receptor- ..
  3. BONE MATRIX AND BONE RESORPTION
    Paul R Odgren; Fiscal Year: 2012
    ..Both ia rats and the human patient have TRAP+, non-resorbing osteoclasts with defective ruffled borders (RB) and defective secretion...
  4. Sirtuin/FOXO Signaling in the Regulation of Bone Mass
    Stavroula Kousteni; Fiscal Year: 2012
    ..They are also expressed in osteoclasts. SIRT1-dependent deacetylation of FOXO1 is required for its anti-apoptotic effects...
  5. Novel, Rapidly Translatable Technologies for Healing Long Bone Segmental Defects
    Christopher H Evans; Fiscal Year: 2010
    ..Runx2, to identify human osteoblasts, and against human tartrate-resistant acid phosphatase, to identify human osteoclasts. Because of our prior experience with the core technologies to be used in this project, the proposal is "shovel ..
  6. Anti-Inflammatory Glycosaminoglycan Ethers for Treatment of Periodontitis
    JUSTIN RODNEY SAVAGE; Fiscal Year: 2013
    ..gingivalis by macrophages. Third, it inhibits P. gingivalis LPS-induced formation of multinucleated osteoclasts from blood monocytes...
  7. Identification of Proteins Important for Male Osteoporosis
    Hong Wen Deng; Fiscal Year: 2013
    ..cells (BMMSCs) and peripheral blood monocytes (PBMs) are precursors for osteoblasts (bone formation cells) and osteoclasts (bone resorption cells), respectively...
  8. Runx Proteins and Sex Steroid Signaling in Bone
    Baruch Frenkel; Fiscal Year: 2009
    ..The anti-resorptive effects of sex steroids are attributable to both direct pro-apoptotic action in osteoclasts and indirect inhibition of bone turnover via poorly understood mechanisms in osteoblasts and other mesenchymal ..
  9. Inhibition of bone formation by Prx1
    Mark S Nanes; Fiscal Year: 2013
    ..Understanding this mechanism will allow us to find new medications that stimulate new bone formation and regeneration of tissue in veterans who suffer from arthritis, aging, and menopause associated fractures. ..
  10. Alcohol-Induced Bone Resorption: The Role of Oxidative Stress
    Martin J J Ronis; Fiscal Year: 2013
    ..In addition, in vivo studies will be conducted to examine the ability of antioxidants to block EtOH-induced bone resorption. ..
  11. Radiation-Induced Osteoporosis in Women with Cancer: Mechanisms and Prevention
    Ted A Bateman; Fiscal Year: 2013
    ..Increased expression of proinflammatory cytokines in the marrow preceded activation of osteoclasts, which was followed by evidence (indicated by phosphoSmad2) of activated transforming growth factor-beta (TGF[..
  12. Mechanisms of Bone Loss from Administration of the Second-Generation Antipsychoti
    KATHERINE JEAN MOTYL; Fiscal Year: 2013
    ..and homeostasis in a manner that results in impaired bone health as well as acts directly on osteoblasts and osteoclasts to disrupt normal skeletal modeling and remodeling...
  13. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    ..of NF-?B (RANK) and CD40, TNFR family members involved in the differentiation and effector functions of osteoclasts and B lymphocytes, respectively...
  14. Osteoclastic Protein-Tyrosine Phosphatase and Resorption
    Kin Hing William Lau; Fiscal Year: 2013
    ..estrogen receptor (ER) 1 signaling through an upregulation of the c-Src-dependent phosphorylation of ER1 in osteoclasts, which in turn suppresses bone resorption in adult female but not male PTP-oc transgenic mice...
  15. The Role of Adipocyte-Induced Inflammation in Prostate Tumor Progression
    AIMALIE LYNNETTE HARDAWAY; Fiscal Year: 2012
    ..Ultimately, these studies should lead to identification of novel signaling pathways and molecular mechanisms predisposing prostate cells to metastasize to bone. ..
  16. Salivary-based Bone-loss Marker Detection Platform for Point-of-Care Screening
    MANAL BESHAY; Fiscal Year: 2012
    ..naturally and continually undergoes turnover with new bone formation by osteoblasts and old bone resorption by osteoclasts at a balanced rate;any imbalance between the two rates results in varying states of abnormal bone turnover such ..
  17. Hematopoietic Stem Cell Transplantation in Osteogenesis Imperfecta
    Meenal Mehrotra; Fiscal Year: 2012
    ..e. HSCs produce blood cells and few other cells like mast cells and osteoclasts, while MSCs generate a number of mesenchymal cells including fibroblasts, adipocytes, chondrocytes and ..
  18. Signal Transduction Mechanism of Osteoclast Differentiation
    Nandini Ghosh-Choudhury; Fiscal Year: 2013
    ..The bone remodeling occurs by concerted action of bone forming osteoblasts and bone resorbing osteoclasts. These functionally opposing cells communicate via a paracrine cell signaling network...
  19. Regulation of glucose metabolism by bone resorption and gamma-carboxylation
    Mathieu Ferron; Fiscal Year: 2012
    ..recently that one mechanism by which osteocalcin is decarboxylated and activated is during bone resorption by osteoclasts. This suggested that osteoclast, the bone-resorbing cell, might also play an important role in the control of ..
  20. Sex Steroids and Runx Signaling in Bone
    Baruch Frenkel; Fiscal Year: 2013
    ..They will decipher cryptic mechanisms of action of existing SERMs, and support the rationale development of novel ones, based on their influence on Runx proteins. ..
  21. Estrogens, androgens, aging, and bone loss in males
    Stavros C Manolagas; Fiscal Year: 2013
    ..that is not capable of stimulating the nuclear- initiated actions of ER1 reproduces the effects of estradiol on osteoclasts and osteoblasts;and is as potent as estradiol in preventing oxidative stress and ovariectomy-induced bone loss, ..
  22. Role of inflammation and cellular stress in the pathogenesis of type 2 diabetes
    Liangyou Rui; Fiscal Year: 2013
    ..The outcome is expected to lead to new therapies for hepatic steatosis and type 2 diabetes by targeting the NIK pathways. ..
  23. Nuclear Events in PTH Action on Bone
    Nicola C Partridge; Fiscal Year: 2013
    ..Moreover, it will define how HDACs contribute to this. In so doing, the data will also provide new perspectives into treatment of disorders of calcium metabolism, cancer-associated bone disease and other bone disorders. ..
  24. Novel Drug VS-105 for Treatment of Osteoporosis
    Jinshyun Ruth Wu-Wong; Fiscal Year: 2013
    ..hormone, receptor activator of nuclear factor-kB ligand, and also via direct effects on osteoblasts and osteoclasts. Despite encouraging data on VDRM's benefits for treating osteoporosis, VDRMs are not used in osteoporosis ..
  25. HYPONATREMIA-INDUCED OSTEOPOROSIS
    Joseph G Verbalis; Fiscal Year: 2010
    ....
  26. Gene-Engineered and Targeted Stem Cell Therapy for Myeloma
    Selvarangan Ponnazhagan; Fiscal Year: 2013
    ..Further, osteoclasts enhance angiogenesis in concert with MM cells largely through the cooperative actions of osteopontin from ..
  27. Purinergic Regulation of Bone Metabolism
    Bruce Neil Cronstein; Fiscal Year: 2013
    ..peripheral blood monocytes and therefore determined whether adenosine A1 receptors also regulated formation of osteoclasts, a related form of multinucleated giant cell...
  28. STRUCTURE OF THE VACUOLAR ATPase
    Stephan Wilkens; Fiscal Year: 2013
    ..In higher eukaryotes, V-type ATPases are also found in the plasma membrane of polarized cells such as osteoclasts and renal epithelial cells...
  29. Pharmacology of Risperidone Effects on Bone Remodeling and Energy Metabolism
    Karen L Houseknecht; Fiscal Year: 2013
    ....
  30. FUNCTION AND REGULATION OF OSTEONECTIN IN BONE
    Anne M Delany; Fiscal Year: 2013
    ..Information obtained from these studies could be used to identify novel targets for therapeutic intervention in the treatment of osteoporosis, and may be used to identify individuals at risk for developing osteoporosis. ..
  31. Role of Gsalpha in Regulating Osteoblast Differentiation
    JOY Y WU; Fiscal Year: 2012
    ..TRAP staining for osteoclasts does not reveal dramatic increase in bone resorption, making a failure of bone formation the more likely ..
  32. Dynamic Mechanisms of Vitamin D-Induced Gene Expression
    J Wesley Pike; Fiscal Year: 2012
    ..a dynamic tissue which is remodeled throughout life as a result of the biological activities of osteoblasts and osteoclasts. The production and survival of these cells as well as their metabolic activities are all highly regulated by ..
  33. ATF4 and Osteoclastogenesis
    Guozhi Xiao; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Osteoclasts (OCLs) are the only bone-resorbing cells that are essential for normal skeletal development and bone remodeling throughout life...
  34. Regulation of Organized Intestinal Lymphoid Tissues by TRANCE/RANKL
    Ifor R Williams; Fiscal Year: 2012
    ..development of lymph nodes, the differentiation of medullary thymic epithelial cells, the differentiation of osteoclasts, and mammary gland lactation, is also present on stromal cells in ILF and PP...
  35. The role of caspase-2 in osteoblast-osteoclast interactions
    DANIELLE ARDEN VICTOR; Fiscal Year: 2013
    ..level of the clinical osteoporosis marker, deoxypyridinoline (DPD), in urine, and increased numbers of osteoclasts, cells responsible for bone resorption...
  36. Molecular Mechanisms in Bone Resorption
    Steven A Lietman; Fiscal Year: 2012
    ..New information about mechanisms of bone resorption may facilitate the development of novel strategies to decrease bone resorption and may lead to new treatments for osteoporosis. ..
  37. Bc12 regulates osteoclast survival
    Junro Yamashita; Fiscal Year: 2010
    ..In such diseases, osteoclast activity typically predominates over osteoblast activity. Hence, suppression of osteoclasts is a therapeutic strategy for the prevention and treatment of degenerative bone diseases...
  38. Connection of Mineral and Energy Metabolism by the Nuclear Receptor PPAR-gamma
    Yihong Wan; Fiscal Year: 2013
    ..Therefore, this investigation will significantly impact the broader scientific, clinical, and patient community. ..
  39. Ethanol Regulates Vacuolar ATPase &PEDF
    Chuhan Chung; Fiscal Year: 2013
    ..This occurs in cells such as osteoclasts where genetic mutations in v-ATPase result in severe skeletal abnormalities and death in humans and in mouse ..
  40. Regulation of IGF-1 and Insulin Signaling by O-GlcNAc Glycosylation
    LAUREN ELIZABETH BALL; Fiscal Year: 2013
    ..and IRS-2, which are critical to the formation of new bone and maintaining coupling between osteoblasts and osteoclasts. Signaling through the IRS proteins to PI3K/Akt and/or the Grb2/ERK pathways is mediated and modulated by ..
  41. Osteoclasts from pluripotent stem cells as vectors to modify bone marrow environm
    Hector L Aguila; Fiscal Year: 2010
    ..development of human ES cells to hematopoiesis towards myeloid development, focusing on conditions to generate osteoclasts. These experiments will test the hypothesis that myeloid cells of human origin derived from modified human ES ..
  42. Effect of MIP-1 delta on Osteoclast Development and Pathological Bone Resorption
    Scott L Kominsky; Fiscal Year: 2010
    ..arthritis and periodontitis, has been shown to enhance the development of bone-destroying cells called osteoclasts (OCL)...
  43. Biomaterials (Mf/Zn/F-BCPs) for osteoporosis therapy
    Yu Zhang; Fiscal Year: 2012
    ..Abstract) Osteoporosis, a silent debilitating bone disease, results when the rate of bone resorption (by osteoclasts) is much greater than the rate of bone formation (by osteoblasts) causing bone loss, deterioration of bone ..
  44. Cathespin K Radioligands for In Vivo Imaging
    Michael R Kilbourn; Fiscal Year: 2012
    ..forms of known high affinity inhibitors of cathepsin K, a cyteine protease that in highly expressed in osteoclasts and that is responsible for type I collagen degradation and bone resorption...
  45. PTHrP Modulation of TRPV1 in Pain Associated with Breast Cancer Bone Metastasis
    AARON DAVID MICKLE; Fiscal Year: 2013
    ..cancer cells secrete high levels of parathyroid hormone-related peptide (PTHrP), which act on osteoblasts and osteoclasts to induce bone lysis/destruction and subsequent release of nutrients and cell signaling molecules that ..
  46. Connexin 43 in Bone Remodeling
    Roberto Civitelli; Fiscal Year: 2013
    ..Like remodeling, modeling requires coordination of osteoblasts (Obl), osteocytes (Ocy) and osteoclasts (Ocl)...
  47. RANKL and Inflammation-associated Bone Loss
    CHARLES A O'BRIEN; Fiscal Year: 2012
    ..b>Osteoclasts are the only cells capable of degrading bone and RANKL is a protein produced by cells that support osteoclast ..
  48. ERK Signaling in Inflammatory Bone Loss
    Francis Young In Lee; Fiscal Year: 2013
    ..Overall impact is high in that we expect to unravel novel anti-osteoclastogenic mechanisms and therapeutic promise of rhCRG in the context of inflammatory osteolysis. ..
  49. ELUCIDATING THE FUNCTION OF MATRIPTASE-ACTIVATED PDGF D IN BONE METASTATIC PROSTA
    ABDO JAMAL NAJY; Fiscal Year: 2012
    ..mediated maturation of PDGF D may activate the tumor cell derived growth factor resulting in the activation of osteoclasts and osteoblasts leading to an aberrant osseous response...
  50. Pre-osteoclast fusion
    Paul R Odgren; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Bone resorption by osteoclasts (OCs) exceeding formation by osteoblasts (OBs) is a biological problem with a central role in widespread and costly disorders, including osteoporosis, osteo- and ..
  51. Molecular Basis of the Anti-inflammatory Action of MAYP/PSTPIP2
    Violeta Chitu; Fiscal Year: 2012
    ..MAYP is selectively expressed in macrophages, mast cells and osteoclasts and is an actin-bundling protein that regulates filopodia formation and macrophage motililty...
  52. Role of Darc-Chemokine Interaction in the Trafficking of Osteoclast Precursors
    Bouchra Edderkaoui; Fiscal Year: 2012
    ..In terms of mechanism by which Darc regulates osteoclasts, our preliminary studies have shown that 1) M-CSF dependent bone marrow cells derived from Darc-knockout (Darc-..
  53. Actions of Parathyroid Hormone (PTH)/PTH Related-Peptide Receptor in Osteocytes
    PAOLA DIVIETI PAJEVIC; Fiscal Year: 2013
    ..lacunae deep within the mineralized matrix of bone and communicate with one another and with osteoblasts and osteoclasts via gap junctions located at the ends of long cytoplasmic processes that course through tunnels (cannalicula) ..
  54. Phosphorylation of PTH1R by TGF-betaRII in Bone Remodeling
    Tao Qiu; Fiscal Year: 2013
    ..This proposal may reveal a previously unrecognized function for T2RII in bone remodeling and a mechanism for PTH to regulate local growth factor at the level of membrane receptor. ..
  55. The use of patient-specific iPS cells to identify osteoclast defects in CMD
    I Ping Chen; Fiscal Year: 2011
    ..applicant plans to use patient-specific iPS cells to study craniometaphyseal dysplasia (CMD) with a focus on osteoclasts (OCs), the bone resorbing cells...
  56. CSF-1 GENE EXPRESSION IN OSTEOCLAST BIOLOGY
    SHERRY L ABBOUD-WERNER; Fiscal Year: 2013
    ..knockout (cKO) of CSF-1 in osteocytes/late osteoblasts also show increased Nox4, osteocyte defects, reduced osteoclasts and bone formation, predisposing to bone loss and fracture with age...
  57. MOLECULAR AND CELLULAR MECHANISMS OF OSTEOPOROSIS
    Stavros C Manolagas; Fiscal Year: 2013
    ..of reactive oxygen species (ROS) amplification by p66shc or ROS attenuation by FoxOs in osteoblasts and osteoclasts to skeletal homeostasis and its deregulation with aging, the role of ROS in the effects estrogens on ..
  58. Genetic Determinants of Physiological Responses to Fluoride in Bone
    Eric T Everett; Fiscal Year: 2012
    ..forms and exposures has been repeatedly shown to have actions on bone matrix and on bone cells (osteoblasts and osteoclasts)...
  59. Coloney Stimulating Factor 1 regulation and role in bone
    KARL LEONARD INSOGNA; Fiscal Year: 2010
    ..Preliminary results from mCSF1 knock out mice indicate that they have increased bone mass and reduced number of osteoclasts. To identify CSF-1 target genes in osteoclasts, we have used a gene profiling approach and found 7 genes ..
  60. Evaluating the role of Thrombospondin-1-CD47 mediated nitric oxide signaling in t
    Sarah Amend; Fiscal Year: 2013
    ..Under homeostatic conditions, bone-resorbing osteoclasts are tightly regulated for healthy bone turnover...
  61. AgRP neurons regulate bone remodeling in aging
    KARL LEONARD INSOGNA; Fiscal Year: 2013
    ..2008), we also predict that increasing ROS exposure of the melanocortin system during aging is a critical contributor to aging-associated bone loss and the pathogenesis of osteoporosis. ..
  62. Complement and Osteoporosis
    Feng Lin; Fiscal Year: 2013
    ..marrow cells from complement receptor-deficient mice had decreased capacity to differentiate into functional osteoclasts. Further, inhibition of complement signaling suppressed human osteoclast differentiation from hematopoietic ..
  63. Amelioration of Immune Cell-Mediated Periodontal Disease
    Toshihisa Kawai; Fiscal Year: 2012
    ..Recent studies demonstrated unequivocally that host immune responses play a key role in activating osteoclasts and promoting bone resorption in periodontal disease...
  64. DEGRADABLE HYDROGELS FOR ORAL DELIVERY OF CALCITONIN
    Jindrich Kopecek; Fiscal Year: 2003
    ..hCT use in osteoporosis therapy are the stimulation of osteoblasts, specific inhibition of bone resorption by osteoclasts, and prevention of fusion of osteoclast precursors...
  65. DEGRADABLE HYDROGELS FOR ORAL DELIVERY OF CALCITONIN
    Jindrich Kopecek; Fiscal Year: 2001
    ..hCT use in osteoporosis therapy are the stimulation of osteoblasts, specific inhibition of bone resorption by osteoclasts, and prevention of fusion of osteoclast precursors...
  66. RANK-Associated Inhibitor (RAIN) in Osteoclast Formation
    Bryant Darnay; Fiscal Year: 2007
    ..Mice deleted of RANKL, RANK, or TRAF6 lack osteoclasts and develop severe osteopetrosis while mice lacking OPG develop osteoporosis...
  67. Innate Immune Bacterial Recognition and Osteoclastogenesis
    Caroline A Genco; Fiscal Year: 2010
    ..In addition, macrophages contribute to bone resorption through their differentiation to osteoclasts (1)...
  68. Is Mitf the Missing Puzzle Linking NFATc1 to Osteoclastogenesis
    Yi Ling Lin; Fiscal Year: 2010
    b>Osteoclasts are bone-resorbing cells essential for maintaining bone mass through modeling and remodeling...
  69. TRAF6 E3 LIGASE FUNCTION IN OSTEOCLASTOGENESIS
    Bryant G Darnay; Fiscal Year: 2010
    ..a central role in the maintenance of the bone homeostasis by regulating the differentiation and activation of osteoclasts. The binding of RANKL to its receptor results in the recruitment of TRAF6, which activates the NF-(B, JNK, p38, ..
  70. ENDOTHELIAL CELLS AND OSTEOCLAST DEVELOPMENT
    Patricia Collin Osdoby; Fiscal Year: 1999
    ..which is established during bone development and maintained thereafter between vascular endothelial cells and osteoclasts (of hematopoietic origin) enables vascular endothelial cells to potentially influence the development and/or ..
  71. Functional Analysis of NHA-oc/NHA2 in vivo
    RICARDO ANIBAL BATTAGLINO; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Bone destruction by osteoclasts is essential for normal bone development...
  72. MICROPHTHALMIA IN OSTEOCLAST DEVELOPMENT
    Katherine Weilbaecher; Fiscal Year: 2002
    ..b>Osteoclasts play an important role in the pathogenesis of osteoporosis, osteopetrosis, and a variety of pathological ..
  73. Function of Phospholipase Cgamma2 in RANKL-Induced Osteoclastogenesis
    Yabing Chen; Fiscal Year: 2010
    ..Pathogenic bone resorption modulated by elevation of osteoclasts is a major cause of bone loss in diseases such as osteoporosis, rheumatoid arthritis and osteolytic bone ..
  74. TAMOXIFEN MODULATES OSTEOCLAST CA++/CALMODULIN SIGNALING
    Jay McDonald; Fiscal Year: 2001
    ..to characterize the rate limiting molecular steps in osteoclast metabolism using chicken, rabbit and human osteoclasts. The specific aims are: I...