当前位置： SCI文献检索 > NATURE MEDICINE期刊下所有文献 > v-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation.

v-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation.

Abstract：

: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. Fusion-mediated giant cell formation is critical for osteoclast maturation; without it, bone resorption is inefficient. To understand how osteoclasts differ from other myeloid lineage cells, we previously compared global mRNA expression patterns in these cells and identified genes of unknown function predominantly expressed in osteoclasts, one of which is the d2 isoform of vacuolar (H(+)) ATPase (v-ATPase) V(0) domain (Atp6v0d2). Here we show that inactivation of Atp6v0d2 in mice results in markedly increased bone mass due to defective osteoclasts and enhanced bone formation. Atp6v0d2 deficiency did not affect differentiation or the v-ATPase activity of osteoclasts. Rather, Atp6v0d2 was required for efficient pre-osteoclast fusion. Increased bone formation was probably due to osteoblast-extrinsic factors, as Atp6v02 was not expressed in osteoblasts and their differentiation ex vivo was not altered in the absence of Atp6v02. Our results identify Atp6v0d2 as a regulator of osteoclast fusion and bone formation, and provide genetic data showing that it is possible to simultaneously inhibit osteoclast maturation and stimulate bone formation by therapeutically targeting the function of a single gene.

journal_name

Nat Med

journal_title

Nature medicine

authors

Lee SH,Rho J,Jeong D,Sul JY,Kim T,Kim N,Kang JS,Miyamoto T,Suda T,Lee SK,Pignolo RJ,Koczon-Jaremko B,Lorenzo J,Choi Y

doi

10.1038/nm1514

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

1403-9

issue

12

eissn

1078-8956

issn

1546-170X

pii

nm1514

journal_volume

12

pub_type

杂志文章

相关文献

NATURE MEDICINE文献大全
  • Cancer genes and the pathways they control.

    abstract：:The revolution in cancer research can be summed up in a single sentence: cancer is, in essence, a genetic disease. In the last decade, many important genes responsible for the genesis of various cancers have been discovered, their mutations precisely identified, and the pathways through which they act characterized. T...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/nm1087

    authors： Vogelstein B,Kinzler KW

    更新日期：2004-08-01 00:00:00

  • T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers.

    abstract：:Recent efforts toward an HIV vaccine focus on inducing broadly neutralizing antibodies, but eliciting both neutralizing antibodies (nAbs) and cellular responses may be superior. Here, we immunized macaques with an HIV envelope trimer, either alone to induce nAbs, or together with a heterologous viral vector regimen to...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-0858-8

    authors： Arunachalam PS,Charles TP,Joag V,Bollimpelli VS,Scott MKD,Wimmers F,Burton SL,Labranche CC,Petitdemange C,Gangadhara S,Styles TM,Quarnstrom CF,Walter KA,Ketas TJ,Legere T,Jagadeesh Reddy PB,Kasturi SP,Tsai A,Yeung BZ

    更新日期：2020-06-01 00:00:00

  • Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants.

    abstract：:Defects in major histocompatibility complex (MHC) class I-restricted antigen presentation are frequently observed in human cancers and result in escape of tumors from cytotoxic T lymphocyte (CTL) immune surveillance in mice. Here, we show the existence of a unique category of CTLs that can prevent this escape. The CTL...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1381

    authors： van Hall T,Wolpert EZ,van Veelen P,Laban S,van der Veer M,Roseboom M,Bres S,Grufman P,de Ru A,Meiring H,de Jong A,Franken K,Teixeira A,Valentijn R,Drijfhout JW,Koning F,Camps M,Ossendorp F,Kärre K,Ljunggren HG,Mel

    更新日期：2006-04-01 00:00:00

  • Dynamics of genetically engineered hematopoietic stem and progenitor cells after autologous transplantation in humans.

    abstract：:Hematopoietic stem and progenitor cells (HSPC) are endowed with the role of generating and maintaining lifelong the extremely diverse pool of blood cells1. Clinically, transplantation of human HSPC from an allogeneic healthy donor or infusion of autologous gene-corrected HSPC can effectively replenish defective blood ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-018-0195-3

    authors： Scala S,Basso-Ricci L,Dionisio F,Pellin D,Giannelli S,Salerio FA,Leonardelli L,Cicalese MP,Ferrua F,Aiuti A,Biasco L

    更新日期：2018-11-01 00:00:00

  • Inhibition of gastric inhibitory polypeptide signaling prevents obesity.

    abstract：:Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with ins...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm727

    authors： Miyawaki K,Yamada Y,Ban N,Ihara Y,Tsukiyama K,Zhou H,Fujimoto S,Oku A,Tsuda K,Toyokuni S,Hiai H,Mizunoya W,Fushiki T,Holst JJ,Makino M,Tashita A,Kobara Y,Tsubamoto Y,Jinnouchi T,Jomori T,Seino Y

    更新日期：2002-07-01 00:00:00

  • Somatic overgrowth associated with overexpression of insulin-like growth factor II.

    abstract：:Overexpression of the normally imprinted fetal insulin-like growth factor II (IGF2) has been implicated in the pathogenesis of the cancer-predisposing Beckwith-Wiedemann syndrome (BWS). We have detected constitutional relaxation of imprinting of IGF2 in four children with somatic overgrowth who do not show diagnostic ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0396-311

    authors： Morison IM,Becroft DM,Taniguchi T,Woods CG,Reeve AE

    更新日期：1996-03-01 00:00:00

  • Deacetylase inhibition promotes the generation and function of regulatory T cells.

    abstract：:Histone/protein deacetylases (HDACs) regulate chromatin remodeling and gene expression as well as the functions of more than 50 transcription factors and nonhistone proteins. We found that administration of an HDAC inhibitor (HDACi) in vivo increased Foxp3 gene expression, as well as the production and suppressive fun...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1652

    authors： Tao R,de Zoeten EF,Ozkaynak E,Chen C,Wang L,Porrett PM,Li B,Turka LA,Olson EN,Greene MI,Wells AD,Hancock WW

    更新日期：2007-11-01 00:00:00

  • TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination.

    abstract：:Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by localized areas of demyelination. Although the etiology and pathogenesis of MS remain largely unknown, it is generally assumed that immune responses to myelin antigens contribute to the disease process. The exact se...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0198-078

    authors： Liu J,Marino MW,Wong G,Grail D,Dunn A,Bettadapura J,Slavin AJ,Old L,Bernard CC

    更新日期：1998-01-01 00:00:00

  • A recombinant Mycobacterium smegmatis induces potent bactericidal immunity against Mycobacterium tuberculosis.

    abstract：:We report the involvement of an evolutionarily conserved set of mycobacterial genes, the esx-3 region, in evasion of bacterial killing by innate immunity. Whereas high-dose intravenous infections of mice with the rapidly growing mycobacterial species Mycobacterium smegmatis bearing an intact esx-3 locus were rapidly l...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2420

    authors： Sweeney KA,Dao DN,Goldberg MF,Hsu T,Venkataswamy MM,Henao-Tamayo M,Ordway D,Sellers RS,Jain P,Chen B,Chen M,Kim J,Lukose R,Chan J,Orme IM,Porcelli SA,Jacobs WR Jr

    更新日期：2011-09-04 00:00:00

  • Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation.

    abstract：:Retinoic acid and arsenic trioxide target the protein stability and transcriptional repression activity of the fusion oncoprotein PML-RARA, resulting in regression of acute promyelocytic leukemia (APL). Phenotypically, retinoic acid induces differentiation of APL cells. Here we show that retinoic acid also triggers gr...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.1891

    authors： Nasr R,Guillemin MC,Ferhi O,Soilihi H,Peres L,Berthier C,Rousselot P,Robledo-Sarmiento M,Lallemand-Breitenbach V,Gourmel B,Vitoux D,Pandolfi PP,Rochette-Egly C,Zhu J,de Thé H

    更新日期：2008-12-01 00:00:00

  • Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions.

    abstract：:Foxp3(+) regulatory T (T(reg)) cells suppress different types of immune responses to help maintain homeostasis in the body. How T(reg) cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of T(reg) cells expressing CXCR5 and Bcl-6 that localize to the germinal cen...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2426

    authors： Chung Y,Tanaka S,Chu F,Nurieva RI,Martinez GJ,Rawal S,Wang YH,Lim H,Reynolds JM,Zhou XH,Fan HM,Liu ZM,Neelapu SS,Dong C

    更新日期：2011-07-24 00:00:00

  • A novel influenza A virus mitochondrial protein that induces cell death.

    abstract：:While searching for alternative reading-frame peptides encoded by influenza A virus that are recognized by CD8+ T cells, we found an abundant immunogenic peptide encoded by the +1 reading frame of PB1. This peptide derives from a novel conserved 87-residue protein, PB1-F2, which has several unusual features compared w...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1201-1306

    authors： Chen W,Calvo PA,Malide D,Gibbs J,Schubert U,Bacik I,Basta S,O'Neill R,Schickli J,Palese P,Henklein P,Bennink JR,Yewdell JW

    更新日期：2001-12-01 00:00:00

  • Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury.

    abstract：:Traumatic spinal cord injury often results in complete loss of voluntary motor and sensory function below the site of injury. The long-term neurological deficits after spinal cord trauma may be due in part to widespread apoptosis of neurons and oligodendroglia in regions distant from and relatively unaffected by the i...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/11387

    authors： Springer JE,Azbill RD,Knapp PE

    更新日期：1999-08-01 00:00:00

  • Inducible cyclooxygenase may have anti-inflammatory properties.

    abstract：:Cyclooxygenase (COX) has two isoforms. Generally, COX 1 is constitutively expressed in most tissues, where it maintains physiological processes; inducible COX 2 is considered a pro-inflammatory enzyme and a chief target for the treatment of inflammatory diseases. Here we present evidence that COX 2 may have anti-infla...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/9550

    authors： Gilroy DW,Colville-Nash PR,Willis D,Chivers J,Paul-Clark MJ,Willoughby DA

    更新日期：1999-06-01 00:00:00

  • Nociceptor sensitization in pain pathogenesis.

    abstract：:The incidence of chronic pain is estimated to be 20-25% worldwide. Few patients with chronic pain obtain complete relief from the drugs that are currently available, and more than half report inadequate relief. Underlying the challenge of developing better drugs to manage chronic pain is incomplete understanding of th...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2235

    authors： Gold MS,Gebhart GF

    更新日期：2010-11-01 00:00:00

  • On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver.

    abstract：:Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal. In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threate...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4146

    authors： Theurl I,Hilgendorf I,Nairz M,Tymoszuk P,Haschka D,Asshoff M,He S,Gerhardt LM,Holderried TA,Seifert M,Sopper S,Fenn AM,Anzai A,Rattik S,McAlpine C,Theurl M,Wieghofer P,Iwamoto Y,Weber GF,Harder NK,Chousterman BG,

    更新日期：2016-08-01 00:00:00

  • Estrogen-dependent and C-C chemokine receptor-2-dependent pathways determine osteoclast behavior in osteoporosis.

    abstract：:Understanding the mechanisms of osteoclastogenesis is crucial for developing new drugs to treat diseases associated with bone loss, such as osteoporosis. Here we report that the C-C chemokine receptor-2 (CCR2) is crucially involved in balancing bone mass. CCR2-knockout mice have high bone mass owing to a decrease in n...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.1945

    authors： Binder NB,Niederreiter B,Hoffmann O,Stange R,Pap T,Stulnig TM,Mack M,Erben RG,Smolen JS,Redlich K

    更新日期：2009-04-01 00:00:00

  • Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study.

    abstract：:Although prognostic gene expression signatures for survival in early-stage lung cancer have been proposed, for clinical application, it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site, blinded validation...

    journal_title：Nature medicine

    pub_type： 杂志文章,多中心研究

    doi：10.1038/nm.1790

    authors： Director's Challenge Consortium for the Molecular Classification of Lung Adenocarcinoma.,Shedden K,Taylor JM,Enkemann SA,Tsao MS,Yeatman TJ,Gerald WL,Eschrich S,Jurisica I,Giordano TJ,Misek DE,Chang AC,Zhu CQ,Strumpf D,Hanash

    更新日期：2008-08-01 00:00:00

  • Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease.

    abstract：:Neurovascular dysfunction substantially contributes to Alzheimer disease. Here, we show that transcriptional profiling of human brain endothelial cells (BECs) defines a subset of genes whose expression is age-independent but is considerably altered in Alzheimer disease, including the homeobox gene MEOX2 (also known as...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1287

    authors： Wu Z,Guo H,Chow N,Sallstrom J,Bell RD,Deane R,Brooks AI,Kanagala S,Rubio A,Sagare A,Liu D,Li F,Armstrong D,Gasiewicz T,Zidovetzki R,Song X,Hofman F,Zlokovic BV

    更新日期：2005-09-01 00:00:00

  • Role of NMDA receptor-dependent activation of SREBP1 in excitotoxic and ischemic neuronal injuries.

    abstract：:Excitotoxic neuronal damage caused by overactivation of N-methyl-D-aspartate glutamate receptors (NMDARs) is thought to be a principal cause of neuronal loss after stroke and brain trauma. Here we report that activation of sterol regulatory element binding protein-1 (SREBP-1) transcription factor in affected neurons i...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2064

    authors： Taghibiglou C,Martin HG,Lai TW,Cho T,Prasad S,Kojic L,Lu J,Liu Y,Lo E,Zhang S,Wu JZ,Li YP,Wen YH,Imm JH,Cynader MS,Wang YT

    更新日期：2009-12-01 00:00:00

  • Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions.

    abstract：:The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing o...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-018-0323-0

    authors： Teixeira VH,Pipinikas CP,Pennycuick A,Lee-Six H,Chandrasekharan D,Beane J,Morris TJ,Karpathakis A,Feber A,Breeze CE,Ntolios P,Hynds RE,Falzon M,Capitanio A,Carroll B,Durrenberger PF,Hardavella G,Brown JM,Lynch AG,Fa

    更新日期：2019-03-01 00:00:00

  • Production of atypical measles in rhesus macaques: evidence for disease mediated by immune complex formation and eosinophils in the presence of fusion-inhibiting antibody.

    abstract：:The severe disease atypical measles occurred when individuals immunized with a poorly protective inactivated vaccine contracted measles, and was postulated to be due to a lack of fusion-inhibiting antibodies. Here, rhesus macaques immunized with formalin-inactivated measles vaccine developed transient neutralizing and...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/9473

    authors： Polack FP,Auwaerter PG,Lee SH,Nousari HC,Valsamakis A,Leiferman KM,Diwan A,Adams RJ,Griffin DE

    更新日期：1999-06-01 00:00:00

  • Patient-derived induced pluripotent stem cells in cancer research and precision oncology.

    abstract：:Together with recent advances in the processing and culture of human tissue, bioengineering, xenotransplantation and genome editing, Induced pluripotent stem cells (iPSCs) present a range of new opportunities for the study of human cancer. Here we discuss the main advantages and limitations of iPSC modeling, and how t...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4238

    authors： Papapetrou EP

    更新日期：2016-12-06 00:00:00

  • Immunophilins and the nervous system.

    abstract：:The search for immunosuppressant drugs to increase the success of organ transplantation led to the discovery of the immunophilins, proteins that interface with a range of signal transduction systems inside cells, especially in the nervous and immune systems. Here we review how these interesting molecules work and cons...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/nm0195-32

    authors： Snyder SH,Sabatini DM

    更新日期：1995-01-01 00:00:00

  • Immunity or tolerance: opposite outcomes of microchimerism from skin grafts.

    abstract：:Solid organ transplants contain small numbers of leukocytes that can migrate into the host and establish long-lasting microchimerism. Although such microchimerism is often associated with graft acceptance and tolerance, it has been difficult to demonstrate a true causal link. Using skin from mutant mice deficient for ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/83393

    authors： Anderson CC,Matzinger P

    更新日期：2001-01-01 00:00:00

  • Genetic clues to the pathogenesis of Parkinson's disease.

    abstract：:Recent years have seen an explosion in the rate of discovery of genetic defects linked to Parkinson's disease. These breakthroughs have not provided a direct explanation for the disease process. Nevertheless, they have helped transform Parkinson's disease research by providing tangible clues to the neurobiology of the...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/nm1068

    authors： Vila M,Przedborski S

    更新日期：2004-07-01 00:00:00

  • Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways.

    abstract：:We evaluated the ability of neonatal porcine islets to engraft and restore glucose control in pancreatectomized rhesus macaques. Although porcine islets transplanted into nonimmunosuppressed macaques were rapidly rejected by a process consistent with cellular rejection, recipients treated with a CD28-CD154 costimulati...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1375

    authors： Cardona K,Korbutt GS,Milas Z,Lyon J,Cano J,Jiang W,Bello-Laborn H,Hacquoil B,Strobert E,Gangappa S,Weber CJ,Pearson TC,Rajotte RV,Larsen CP

    更新日期：2006-03-01 00:00:00

  • Time to 'walk the walk' about industry ties to enhance health.

    abstract：:Overwhelming evidence that relationships between universities, physicians and the medical products industry benefit patients explains the ubiquitous calls to encourage such relationships. Yet accumulating 'conflict of interest' regulations in academic health centers, government and industry have had the opposite effec...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0411-437

    authors： Stossel TP,Stell LK

    更新日期：2011-04-01 00:00:00

  • Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer.

    abstract：:Lung cancer is the leading cause of death from cancer in the US and the world. The high mortality rate (80-85% within 5 years) results, in part, from a lack of effective tools to diagnose the disease at an early stage. Given that cigarette smoke creates a field of injury throughout the airway, we sought to determine i...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1556

    authors： Spira A,Beane JE,Shah V,Steiling K,Liu G,Schembri F,Gilman S,Dumas YM,Calner P,Sebastiani P,Sridhar S,Beamis J,Lamb C,Anderson T,Gerry N,Keane J,Lenburg ME,Brody JS

    更新日期：2007-03-01 00:00:00

  • Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis.

    abstract：:Peroxisome proliferator-activated receptor-delta (PPAR-delta; also known as PPAR-beta) is expressed at high levels in colon tumors, but its contribution to colon cancer is unclear. We examined the role of PPAR-delta in colon carcinogenesis using PPAR-delta-deficient (Ppard(-/-)) mice. In both the Min mutant and chemic...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1026

    authors： Harman FS,Nicol CJ,Marin HE,Ward JM,Gonzalez FJ,Peters JM

    更新日期：2004-05-01 00:00:00