Evidence for the presence of a proton pump of the vacuolar H(+)-ATPase type in the ruffled borders of osteoclasts

Microsomal membrane vesicles prepared either from chicken medullary bone or isolated osteoclasts were shown to have ATP-dependent H(+)- transport activity. This activity was N-ethylmaleimide-sensitive but resistant to oligomycin and orthovanadate, suggesting a vacuolar-type ATPase. Furthermore, immunological cross-reactivity of 60- and 70-kD osteoclast membrane antigens with Neurospora crassa vacuolar ATPase was observed when analyzed by immunoblotting. Same antibodies labeled only osteoclasts in chicken and rat bone in immunohistochemistry. Immunoelectronmicroscopy localized these antigens in apical membranes of rat osteoclasts and kidney intercalated cells of inner stripe of outer medulla. Pretreatment of animals with parathyroid hormone enhanced the immunoreaction in the apical membranes of osteoclasts. No immunoreaction was seen in osteoclasts when antibodies against gastric H+,K(+)-ATPase were used. These results suggest that osteoclast resorbs bone by secreting protons through vacuolar H(+)-ATPase.

• Publication year

  1990

• Venue

  Journal of Cell Biology

• Publication date

  1990-09-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/JCB.111.3.1305PMID 2144003PMCID 2116263
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Immunoelectron microscopic localization of carbonic anhydrase III in rat skeletal muscle

  2004cited by this paper
• Ultracytochemical evidence for a proton-pump adenosine triphosphatase in chick osteoclasts

  2004cited by this paper
• Structure, molecular genetics, and evolution of vacuolar H+-ATPases

  1989cited by this paper
• Osteoclastic bone resorption by a polarized vacuolar proton pump.

  1989cited by this paper
• Consecutive expression of carbonic anhydrase isoenzymes during development of rat liver and skeletal muscle differentiation.

  1989cited by this paper
• Organization of osteoclast microfilaments during the attachment to bone surface in vitro

  1989cited by this paper
• Isolation of genes encoding the Neurospora vacuolar ATPase. Analysis of vma-2 encoding the 57-kDa polypeptide and comparison to vma-1.

  1988cited by this paper
• Cellular biology and biochemical mechanism of bone resorption. A review of recent developments on the formation, activation, and mode of action of osteoclasts.

  1988cited by this paper
• Isolation of genes encoding the Neurospora vacuolar ATPase. Analysis of vma-1 encoding the 67-kDa subunit reveals homology to other ATPases.

  1988cited by this paper
• Evidence for a high and specific concentration of (Na+,K+)ATPase in the plasma membrane of the osteoclast.

  1986cited by this paper
• Characterization of the subunit structure of the maize tonoplast ATPase. Immunological and inhibitor binding studies.

  1986cited by this paper
• Humoral and ionic regulation of osteoclast acidity

  1986cited by this paper
• Structural studies of the vacuolar membrane ATPase from Neurospora crassa and comparison with the tonoplast membrane ATPase from Zea mays.

  1986cited by this paper
• Acidification of the endocytic and exocytic pathways.

  1986cited by this paper
• Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border

  1985cited by this paper
• A new method of preparing gold probes for multiple-labeling cytochemistry.

  1985cited by this paper
• An electrogenic proton-translocating adenosine triphosphatase from bovine kidney medulla.

  1984cited by this paper
• High active isoenzyme of carbonic anhydrase in rat calvaria osteoclasts

  1983cited by this paper
• The lysosomal proton pump is electrogenic.

  1983cited by this paper
• Use of colloidal gold particles in double-labeling immunoelectron microscopy of ultrathin frozen tissue sections

  1981cited by this paper
• Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.

  1979cited by this paper
• Ultrastructural localization of intracellular antigens by the use of protein A-gold complex.

  1978cited by this paper
• Characterization of gastric mucosal membranes. IX. Fractionation and purification of K+-ATPase-containing vesicles by zonal centrifugation and free-flow electrophoresis technique.

  1977cited by this paper
• THE EFFECTS OF PARATHYROID HORMONE, COLCHICINE, AND CALCITONIN ON THE ULTRASTRUCTURE AND THE ACTIVITY OF OSTEOCLASTS IN ORGAN CULTURE

  1974cited by this paper
• A TECHNIQUE FOR ULTRACRYOTOMY OF CELL SUSPENSIONS AND TISSUES

  1973cited by this paper
• The sulphatase of ox liver: XV. Changes in the properties of sulphatase A in the presence of substrate

  1970cited by this paper
• The sulphatase of ox liver. II. The purification and properties of sulphatase A.

  1953cited by this paper
• Protein measurement with the Folin phenol reagent.

  1951cited by this paper
• A method for the rapid determination of alkaline phosphates with five cubic millimeters of serum.

  1946cited by this paper
• A METHOD FOR RAPID DETERMINATION OF ALKALINE PHOSPHATASE WITH FIVE CUBIC MILLILITERS OF SERUM

  1946influential reference
• The effects

  year unknowncited by this paper

• Pathophysiology of bone remodelling cycle: Role of immune system and lipids.

  2025cites this paper
• The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease

  2025cites this paper
• Cell fusion dynamics: mechanisms of multinucleation in osteoclasts and macrophages

  2024cites this paper
• Lysosomal biogenesis and function in osteoclasts: a comprehensive review

  2024cites this paper
• Biomaterial Cues for Regulation of Osteoclast Differentiation and Function in Bone Regeneration

  2024cites this paper
• [Treatment options for external inflammatory root resorption].

  2023cites this paper
• The Emerging Role of the Mitochondrial Respiratory Chain in Skeletal Aging

  2023cites this paper
• Melatonin Attenuates RANKL-Induced Osteoclastogenesis via Inhibition of Atp6v0d2 and DC-STAMP through MAPK and NFATc1 Signaling Pathways

  2022cites this paper
• Cycloastragenol Attenuates Osteoclastogenesis and Bone Loss by Targeting RANKL-Induced Nrf2/Keap1/ARE, NF-κB, Calcium, and NFATc1 Pathways

  2022cites this paper
• Multinucleated Giant Cells: Current Insights in Phenotype, Biological Activities, and Mechanism of Formation

  2022cites this paper
• Emerging insights on the role of V‐ATPase in human diseases: Therapeutic challenges and opportunities

  2021cites this paper
• Targeted inhibition of ATP5B gene prevents bone erosion in collagen-induced arthritis by inhibiting osteoclastogenesis.

  2021cites this paper
• Pathophysiological mechanisms of root resorption after dental trauma: a systematic scoping review

  2021cites this paper
• Plasma Membrane Receptors Involved in the Binding and Response of Osteoclasts to Noncellular Components of the Bone

  2021cites this paper
• Cellular Ionic Homeostatic Processes in Osteoclastic Bone Resorption

  2020cites this paper
• Osteoclasts in Cardiovascular Calcification

  2020cites this paper
• Specialized Roles for Actin in Osteoclasts: Unanswered Questions and Therapeutic Opportunities

  2019influential citation
• In Vivo Multicolor Imaging with Fluorescent Probes Revealed the Dynamics and Function of Osteoclast Proton Pumps

  2019cites this paper
• Exploring the Interface between Inflammatory and Therapeutic Glucocorticoid Induced Bone and Muscle Loss

  2019cites this paper
• Technologies, Tools, and Genetic Models to Study Osteoclasts

  2019cites this paper
• Membrane trafficking in osteoclasts and implications for osteoporosis

  2019cites this paper
• Regulation of Schwann cells and osteoclasts with an emphasis on NF1-deficient cells

  2019cites this paper
• Quercitrin Nanocoated Implant Surfaces Reduce Osteoclast Activity In Vitro and In Vivo

  2018cites this paper
• 73-deoxychondropsin A : a novel inhibitor of bone resorption sourced from a Great Barrier Reef sponge

  2018cites this paper
• ARAP1 Bridges Actin Dynamics and AP-3-Dependent Membrane Traffic in Bone-Digesting Osteoclasts

  2018cites this paper
• The effects of soluble activin type IIB receptor on bone formation and body composition

  2018cites this paper
• The effect of surface immobilized NBD peptide on osteoclastogenesis of rough titanium plates in vitro and osseointegration of rough titanium implants in ovariectomized rats in vivo

  2018cites this paper
• Cooperative electrogenic proton transport pathways in the plasma membrane of the proton-secreting osteoclast

  2018cites this paper
• Current Understanding of RANK Signaling in Osteoclast Differentiation and Maturation

  2017cites this paper
• Control of non-apoptotic nurse cell death by engulfment genes in Drosophila

  2017cites this paper
• The Cytoskeleton Architecture of Algivorous Protoplast Feeders (Viridiraptoridae, Rhizaria) Indicates Actin-Guided Perforation of Prey Cell Walls.

  2017cites this paper
• ClC-7/Ostm1 contribute to the ability of tea polyphenols to maintain bone homeostasis in C57BL/6 mice, protecting against fluorosis

  2017cites this paper
• The Cell Biology and Role of Resorptive Cells in Diseases: A Review

  2017cites this paper
• Resorptive Cells in Health and Disease

  2016cites this paper
• Extracellular Iron is a Modulator of the Differentiation of Osteoclast Lineage Cells

  2016cites this paper
• Biochemical and functional properties of mammalian bone alkaline phosphatase isoforms during osteogenesis

  2016cites this paper
• 骨の組織・微細構造 ──顕微解剖学的知見──

  2016cites this paper
• Autophagy-linked FYVE containing protein WDFY3 interacts with TRAF6 and modulates RANKL-induced osteoclastogenesis.

  2016cites this paper
• Monocytes/Macrophages Upregulate the Hyaluronidase HYAL1 and Adapt Its Subcellular Trafficking to Promote Extracellular Residency upon Differentiation into Osteoclasts

  2016cites this paper
• Extracellular fluid flow and chloride content modulate H+ transport by osteoclasts

  2015cites this paper
• Effect of calcium ions on human calcitonin. Possible implications for bone resorption by osteoclasts

  2015cites this paper
• An adult osteopetrosis model in medaka reveals the importance of osteoclast function for bone remodeling in teleost fish.

  2015cites this paper
• Inhibition of RANKL‐dependent cellular fusion in pre‐osteoclasts by amiloride and a NHE10‐specific monoclonal antibody

  2015cites this paper
• VU Research Portal Functional differences between site-specific osteoclasts

  2015cites this paper
• Hypoxic regulation of osteoclast differentiation and bone resorption activity

  2015cites this paper
• Proteomic study of different culture medium serum volume fractions on RANKL-dependent RAW264.7 cells differentiating into osteoclasts

  2015cites this paper
• Mouse ENU mutagenesis and molecular genetics approach to identify novel regulating bone homeostasis

  2015cites this paper
• Protein Modifications in Pathogenic Dysregulation of Signaling

  2015cites this paper
• NF-κB Signaling in Osteoclastogenesis

  2015cites this paper
• Characterization of Functional Reprogramming during Osteoclast Development Using Quantitative Proteomics and mRNA Profiling

  2014cites this paper
• Modulating the Transcriptional Activity of Beta-Catenin During the Osteogenic Differentiation of Embryonic Stem Cells

  2014cites this paper
• Diversity of proton pumps in osteoclasts: V-ATPase with a3 and d2 isoforms is a major form in osteoclasts.

  2014cites this paper
• Mirkka Hirvonen VESICULAR TRAFFICKING IN OSTEOCLASTS

  2014cites this paper
• Mechanistic interpretation of artificial neural network‐based QSAR model for prediction of cathepsin K inhibition potency

  2014cites this paper
• Atividade osteoclástica na superfície de hidroxiapatite nano e microestruturada modulada pela presença de inibidores da bomba de protões

  2014cites this paper
• Roles of ion transport in control of cell motility.

  2013cites this paper
• CHARACTERIZATION OF THE EFFECTS OF PROTON PUMP INHIBITORS ON BONE METABOLISM : IN VITRO STUDY IN CO-CULTURES OF OSTEOCLASTS AND BREAST CANCER CELLS AND IN CULTURES OF OSTEOBLASTS

  2013cites this paper
• Development of Analytical Techniques to Monitor Bone Penetration in 3D via Computer Tomography Analysis.

  2013cites this paper
• Differential regulation of HIF-mediated pathways increases mitochondrial metabolism and ATP production in hypoxic osteoclasts

  2013cites this paper
• Mechanisms controlling vacuolar H+-adenosine triphosphatase activity: targets for the development of new therapeutic agents for the management of osteoporosis

  2013cites this paper
• CHARACTERIZATION OF THE EFFECTS OF PROTON PUMP INHIBITORS ON BONE METABOLISM: IN VITRO STUDY IN CO- CULTURES OF OSTEOCLASTS AND BREAST CANCER CELLS AND IN CULTURES OF OSTEOBLASTS

  2013cites this paper
• Novel perspectives on the transcytotic route in osteoclasts

  2013cites this paper
• Macrophages and Related Cells

  2013cites this paper
• Lipopolysaccharide induces multinuclear cell from RAW264.7 line with increased phagocytosis activity.

  2012cites this paper
• Suture compression induced bone resorption with intensified MMP-1 and 13 expressions.

  2012cites this paper
• Extract of Magnoliae Flos inhibits ovariectomy-induced osteoporosis by blocking osteoclastogenesis and reducing osteoclast-mediated bone resorption.

  2012cites this paper
• Osteopetrosis Mutation R444L Causes Endoplasmic Reticulum Retention and Misprocessing of Vacuolar H+-ATPase a3 Subunit*

  2012cites this paper
• Recent trends in cancer drug resistance reversal strategies using nanoparticles

  2012cites this paper
• Enoxacin Directly Inhibits Osteoclastogenesis without Inducing Apoptosis*

  2012cites this paper
• pH regulators in invadosomal functioning: proton delivery for matrix tasting.

  2012cites this paper
• V‐ATPase subunit ATP6AP1 (Ac45) regulates osteoclast differentiation, extracellular acidification, lysosomal trafficking, and protease exocytosis in osteoclast‐mediated bone resorption

  2012cites this paper
• Protein kinase C–delta deficiency perturbs bone homeostasis by selective uncoupling of cathepsin K secretion and ruffled border formation in osteoclasts

  2012cites this paper
• Anti-Myeloma Effects of the Novel Anthracycline Derivative INNO-206

  2012cites this paper
• Response of Osteoclasts to Titanium Surfaces with Increasing Surface Roughness: An In Vitro Study

  2012cites this paper
• Reversal effects of pantoprazole on multidrug resistance in human gastric adenocarcinoma cells by down‐regulating the V‐ATPases/mTOR/HIF‐1α/P‐gp and MRP1 signaling pathway in vitro and in vivo

  2012cites this paper
• Rab13 Is Upregulated During Osteoclast Differentiation and Associates with Small Vesicles Revealing Polarized Distribution in Resorbing Cells

  2012cites this paper
• Subunit a 3-ATPase + Misprocessing of Vacuolar H Endoplasmic Reticulum Retention and Osteopetrosis Mutation R 444 L Causes Molecular Bases of Disease :

  2012cites this paper
• Potential of the Osteoclast’s Proton Pump as a Drug Target in Osteoporosis

  2011cites this paper
• Bone matrix regulates osteoclast differentiation and annexin A8 gene expression

  2011cites this paper
• Osteoclast and Osteoblast Activities on Carbonate Apatite Plates in Cell Cultures

  2011cites this paper
• Modulação do transporte de prótons em osteoclastos: efeitos da acidose e do fluxo de fluido extracelular.

  2011cites this paper
• Polarized osteoclasts put marks of tartrate-resistant acid phosphatase on dentin slices--a simple method for identifying polarized osteoclasts.

  2011cites this paper
• Local injection/induction of osteoclasts for the treatment of calcified tendinitis.

  2011cites this paper
• Blocking of sodium and potassium ion-dependent adenosine triphosphatase-α1 with ouabain and vanadate suppresses cell-cell fusion during RANKL-mediated osteoclastogenesis.

  2011cites this paper
• ATP6v0d2 deficiency increases bone mass, but does not influence ovariectomy-induced bone loss.

  2010cites this paper
• The vacuolar ATPase in bone cells: a potential therapeutic target in osteoporosis

  2010cites this paper
• Elucidating differences in osteoclast activation mechanisms : looking for targets to prevent pathological bone resorption.

  2010cites this paper
• Nouvelles cibles thérapeutiques dans l’ostéoporose

  2010cites this paper
• Expression of proteases in giant cell lesions of the jaws, tendon sheath and salivary glands.

  2010cites this paper
• A Rationale for Osteoclast Selectivity of Inhibiting the Lysosomal V-ATPase a3 Isoform

  2010cites this paper
• Inhibition of Osteoclast Bone Resorption by Disrupting Vacuolar H+-ATPase a3-B2 Subunit Interaction*

  2010cites this paper
• Acid-base Balance and Oxidative Metabolism in Calcified Tissues

  2010cites this paper
• Degradation of hydroxyapatite in vivo and in vitro requires osteoclastic sodium-bicarbonate co-transporter NBCn1.

  2010cites this paper
• Direct Bone Destruction by Neutrophils in Collagen-induced Arthritis Treated with Bisphosphonates

  2010cites this paper
• The unobtrusive majority: mononucleated bone resorbing cells in teleost fish and mammals

  2010cites this paper
• New treatment targets in osteoporosis.

  2010cites this paper
• Targeted disruption of the Cl−/HCO3− exchanger Ae2 results in osteopetrosis in mice

  2009cites this paper
• Transcriptome and proteome analysis of osteocytes treated with nitrogen-containing bisphosphonates.

  2009cites this paper
• A comparative view on mechanisms and functions of skeletal remodelling in teleost fish, with special emphasis on osteoclasts and their function

  2009cites this paper
• INTRACELLULAR MEMBRANE TRAFFICKING IN OSTEOCLASTS THE ROLE OF DIRECT RAB PROTEIN – RAC 1 INTERACTIONS IN THE TARGETING OF INTRACELLULAR VESICLES

  2009cites this paper