Osteoclast progenitors reside in the peroxisome proliferator-activated receptor γ-expressing bone marrow cell population.

Abstract:

:Osteoclasts are bone-resorbing cells essential for skeletal development, homeostasis, and regeneration. They derive from hematopoietic progenitors in the monocyte/macrophage lineage and differentiate in response to RANKL. However, the precise nature of osteoclast progenitors is a longstanding and important question. Using inducible peroxisome proliferator-activated receptor γ (PPARγ)-tTA TRE-GFP (green fluorescent protein) reporter mice, we show that osteoclast progenitors reside specifically in the PPARγ-expressing hematopoietic bone marrow population and identify the quiescent PPARγ(+) cells as osteoclast progenitors. Importantly, two PPARγ-tTA TRE-Cre-controlled genetic models provide compelling functional evidence. First, Notch activation in PPARγ(+) cells causes high bone mass due to impaired osteoclast precursor proliferation. Second, selective ablation of PPARγ(+) cells by diphtheria toxin also causes high bone mass due to decreased osteoclast numbers. Furthermore, PPARγ(+) cells respond to both pathological and pharmacological resorption-enhancing stimuli. Mechanistically, PPARγ promotes osteoclast progenitors by activating GATA2 transcription. These findings not only identify the long-sought-after osteoclast progenitors but also establish unprecedented tools for their visualization, isolation, characterization, and genetic manipulation.

journal_name

Mol Cell Biol

authors

Wei W,Zeve D,Wang X,Du Y,Tang W,Dechow PC,Graff JM,Wan Y

doi

10.1128/MCB.05979-11

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

4692-705

issue

23

eissn

0270-7306

issn

1098-5549

pii

MCB.05979-11

journal_volume

31

pub_type

杂志文章
  • Distinct subclasses of small GTPases interact with guanine nucleotide exchange factors in a similar manner.

    abstract::The Ras-related GTPases are small, 20- to 25-kDa proteins which cycle between an inactive GDP-bound form and an active GTP-bound state. The Ras superfamily includes the Ras, Rho, Ran, Arf, and Rab/YPT1 families, each of which controls distinct cellular functions. The crystal structures of Ras, Rac, Arf, and Ran reveal...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.12.7444

    authors: Day GJ,Mosteller RD,Broek D

    更新日期:1998-12-01 00:00:00

  • Mechanism of R-loop formation at immunoglobulin class switch sequences.

    abstract::R-loops have been described in vivo at the immunoglobulin class switch sequences and at prokaryotic and mitochondrial origins of replication. However, the biochemical mechanism and determinants of R-loop formation are unclear. We find that R-loop formation is nearly eliminated when RNase T(1) is added during transcrip...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01251-07

    authors: Roy D,Yu K,Lieber MR

    更新日期:2008-01-01 00:00:00

  • DNA sequence, structure, and tyrosine kinase activity of the Drosophila melanogaster Abelson proto-oncogene homolog.

    abstract::We report our molecular characterization of the Drosophila melanogaster Abelson gene (abl), a gene in which recessive loss-of-function mutations result in lethality at the pupal stage of development. This essential gene consists of 10 exons extending over 26 kilobase pairs of genomic DNA. The DNA sequence encodes a pr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.2.843

    authors: Henkemeyer MJ,Bennett RL,Gertler FB,Hoffmann FM

    更新日期:1988-02-01 00:00:00

  • Identification of a novel isoform of the retinoic acid receptor gamma expressed in the mouse embryo.

    abstract::Retinoic acid is known to have profound effects on developmental processes. It has been implicated as a putative morphogen in the developing chick limb bud and regenerating amphibian limb blastema and has been demonstrated to have powerful teratogenic effects in mammals, including humans. Recently, three specific reti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.5.2335

    authors: Giguère V,Shago M,Zirngibl R,Tate P,Rossant J,Varmuza S

    更新日期:1990-05-01 00:00:00

  • Ras-GAP controls Rho-mediated cytoskeletal reorganization through its SH3 domain.

    abstract::Proteins of the Ras superfamily, Ras, Rac, Rho, and Cdc42, control the remodelling of the cortical actin cytoskeleton following growth factor stimulation. A major regulator of Ras, Ras-GAP, contains several structural motifs, including an SH3 domain and two SH2 domains, and there is evidence that they harbor a signall...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.9.5567

    authors: Leblanc V,Tocque B,Delumeau I

    更新日期:1998-09-01 00:00:00

  • Purification and characterization of nucleolin and its identification as a transcription repressor.

    abstract::Expression of the acute-phase response genes, such as that for alpha-1 acid glycoprotein (AGP), involves both positive and negative transcription factors. A positive transcription factor, AGP/EBP, and a negative transcription factor, factor B, have been identified as the two most important factors responsible for the ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.9.6068

    authors: Yang TH,Tsai WH,Lee YM,Lei HY,Lai MY,Chen DS,Yeh NH,Lee SC

    更新日期:1994-09-01 00:00:00

  • Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2.

    abstract::The product of the c-myc proto-oncogene is an important positive regulator of cell growth and proliferation. Recently, c-Myc has also been demonstrated to be a potent inducer of apoptosis when expressed in the absence of serum or growth factors. To further examine Myc-induced apoptosis, we coexpressed the proto-oncoge...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.4.2432

    authors: Wagner AJ,Small MB,Hay N

    更新日期:1993-04-01 00:00:00

  • Properties and possible functions of the adenylate cyclase in plasma membranes of Saccharomyces cerevisiae.

    abstract::We have examined the possible role of adenosine 3',5'-phosphate (cAMP) in functions associated with the plasma membranes of Saccharomyces cerevisiae. Purified membranes from this source contained an adenylate cyclase which was insensitive to activation by fluoride or guanine nucleotides, only weakly responsive to chan...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.12.1481

    authors: Jaynes PK,McDonough JP,Mahler HR

    更新日期:1982-12-01 00:00:00

  • Inhibition of phorbol ester-receptor binding by a factor from human serum.

    abstract::The inhibition of receptor binding of [3H]phorbol-12,13-dibutyrate (PDBu) by a factor from human serum was characterized. The serum factor inhibited [3H]PDBu binding in intact monolayer cultures of the rat embryo cell line CREF N and in a subcellular system containing membranes from these cells. Inhibition occurred at...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.5.545

    authors: Horowitz AD,Greenebaum E,Nicolaides M,Woodward K,Weinstein IB

    更新日期:1982-05-01 00:00:00

  • Mitogenic effects of the proto-oncogene and oncogene forms of c-H-ras DNA in human diploid fibroblasts.

    abstract::Nuclear microinjection of c-H-ras DNA induced DNA synthesis in reversibly nonproliferating quiescent human cells. The proto-oncogene and oncogene forms were equally effective inducers. In contrast, c-H-ras DNA either alone or in combination with the adenovirus E1A gene did not cause terminally nondividing senescent ce...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.8.2990

    authors: Lumpkin CK,Knepper JE,Butel JS,Smith JR,Pereira-Smith OM

    更新日期:1986-08-01 00:00:00

  • The notch intracellular domain can function as a coactivator for LEF-1.

    abstract::Notch signaling commences with two ligand-mediated proteolysis events that release the Notch intracellular domain, NICD, from the plasma membrane. NICD then translocates into the nucleus and interacts with the DNA binding protein CSL to activate transcription. We found that NICD expression also potentiates activity of...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.22.7537-7544.2001

    authors: Ross DA,Kadesch T

    更新日期:2001-11-01 00:00:00

  • Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus.

    abstract::cDNAs for the murine lyn protein tyrosine kinase gene were cloned from mouse bone marrow-derived monocytic cells. Comparison of the human and murine genes demonstrated a 94% homology in peptide sequence. Comparable to the human gene, murine lyn was found to be expressed in myeloid and B-lymphoid lineage cells. During ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.5.2391

    authors: Yi TL,Bolen JB,Ihle JN

    更新日期:1991-05-01 00:00:00

  • Imprinted Nesp55 influences behavioral reactivity to novel environments.

    abstract::Genomic imprinting results in parent-of-origin-dependent monoallelic expression of selected genes. Although their importance in development and physiology is recognized, few imprinted genes have been investigated for their effects on brain function. Gnas is a complex imprinted locus whose gene products are involved in...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.8.3019-3026.2005

    authors: Plagge A,Isles AR,Gordon E,Humby T,Dean W,Gritsch S,Fischer-Colbrie R,Wilkinson LS,Kelsey G

    更新日期:2005-04-01 00:00:00

  • Retroviral transcriptional regulation and embryonic stem cells: war and peace.

    abstract::Retroviruses have evolved complex transcriptional enhancers and promoters that allow their replication in a wide range of tissue and cell types. Embryonic stem (ES) cells, however, characteristically suppress transcription of proviruses formed after infection by exogenous retroviruses and also of most members of the v...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章,评审

    doi:10.1128/MCB.01293-14

    authors: Schlesinger S,Goff SP

    更新日期:2015-03-01 00:00:00

  • DNA repair and transcriptional deficiencies caused by mutations in the Drosophila p52 subunit of TFIIH generate developmental defects and chromosome fragility.

    abstract::The transcription and DNA repair factor TFIIH is composed of 10 subunits. Mutations in the XPB, XPD, and p8 subunits are genetically linked to human diseases, including cancer. However, no reports of mutations in other TFIIH subunits have been reported in higher eukaryotes. Here, we analyze at genetic, molecular, and ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00030-07

    authors: Fregoso M,Lainé JP,Aguilar-Fuentes J,Mocquet V,Reynaud E,Coin F,Egly JM,Zurita M

    更新日期:2007-05-01 00:00:00

  • A novel Rb- and p300-binding protein inhibits transactivation by MyoD.

    abstract::The retinoblastoma protein (Rb) regulates both the cell cycle and tissue-specific transcription, by modulating the activity of factors that associate with its A-B and C pockets. In skeletal muscle, Rb has been reported to regulate irreversible cell cycle exit and muscle-specific transcription. To identify factors inte...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.23.8903-8915.2000

    authors: MacLellan WR,Xiao G,Abdellatif M,Schneider MD

    更新日期:2000-12-01 00:00:00

  • CtBP and associated LSD1 are required for transcriptional activation by NeuroD1 in gastrointestinal endocrine cells.

    abstract::Gene expression programs required for differentiation depend on both DNA-bound transcription factors and surrounding histone modifications. Expression of the basic helix-loop-helix (bHLH) protein NeuroD1 is restricted to endocrine cells in the gastrointestinal (GI) tract, where it is important for endocrine differenti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01600-13

    authors: Ray SK,Li HJ,Metzger E,Schüle R,Leiter AB

    更新日期:2014-06-01 00:00:00

  • The CDK7-cycH-p36 complex of transcription factor IIH phosphorylates p53, enhancing its sequence-specific DNA binding activity in vitro.

    abstract::Phosphorylation is believed to be one of the mechanisms by which p53 becomes activated or stabilized in response to cellular stress. Previously, p53 was shown to interact with three components of transcription factor IIH (TFIIH): excision repair cross-complementing types 2 and 3 (ERCC2 and ERCC3) and p62. This communi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.10.5923

    authors: Lu H,Fisher RP,Bailey P,Levine AJ

    更新日期:1997-10-01 00:00:00

  • Death-associated protein kinase phosphorylates ZIP kinase, forming a unique kinase hierarchy to activate its cell death functions.

    abstract::The death-associated protein (DAP) kinase family includes three protein kinases, DAP kinase, DAP kinase-related protein 1, and ZIP kinase, which display 80% amino acid identity within their catalytic domains and are functionally linked to common subcellular changes occurring during cell death, such as the process of m...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.19.8611-8626.2004

    authors: Shani G,Marash L,Gozuacik D,Bialik S,Teitelbaum L,Shohat G,Kimchi A

    更新日期:2004-10-01 00:00:00

  • The two Drosophila telomeric transposable elements have very different patterns of transcription.

    abstract::The transposable elements HeT-A and TART constitute the telomeres of Drosophila chromosomes. Both are non-long terminal repeat (LTR) retrotransposons, sharing the remarkable property of transposing only to chromosome ends. In addition, strong sequence similarity of their gag proteins indicates that these coding region...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.1.873

    authors: Danilevskaya ON,Traverse KL,Hogan NC,DeBaryshe PG,Pardue ML

    更新日期:1999-01-01 00:00:00

  • Regulation of Rous sarcoma virus RNA splicing and stability.

    abstract::Only a fraction of retroviral primary transcripts are spliced to subgenomic mRNAs; the unspliced transcripts are transported to the cytoplasm for packaging into virions and for translation of the gag and pol genes. We identified cis-acting sequences within the gag gene of Rous sarcoma virus (RSV) which negatively regu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.11.4858

    authors: Arrigo S,Beemon K

    更新日期:1988-11-01 00:00:00

  • A novel c-fgr exon utilized in Epstein-Barr virus-infected B lymphocytes but not in normal monocytes.

    abstract::The fgr proto-oncogene encodes a nonreceptor protein-tyrosine kinase, designated p55c-fgr. In this study, we have isolated human fgr cDNA molecules from normal monocyte mRNA templates. Nucleotide sequence analysis of the longest fgr cDNA revealed a 5' untranslated region of 927 bp which included two Alu-like repeats a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.3.1500

    authors: Gutkind JS,Link DC,Katamine S,Lacal P,Miki T,Ley TJ,Robbins KC

    更新日期:1991-03-01 00:00:00

  • Removal of C-terminal SRC kinase from the immune synapse by a new binding protein.

    abstract::The Csk tyrosine kinase negatively regulates the Src family kinases Lck and Fyn in T cells. Engagement of the T-cell antigen receptor results in a removal of Csk from the lipid raft-associated transmembrane protein PAG/Cbp. Instead, Csk becomes associated with an approximately 72-kDa tyrosine-phosphorylated protein, w...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.6.2227-2241.2005

    authors: Rahmouni S,Vang T,Alonso A,Williams S,van Stipdonk M,Soncini C,Moutschen M,Schoenberger SP,Mustelin T

    更新日期:2005-03-01 00:00:00

  • Dimerization in vivo and inhibition of the nonreceptor form of protein tyrosine phosphatase epsilon.

    abstract::cyt-PTP epsilon is a naturally occurring nonreceptor form of the receptor-type protein tyrosine phosphatase (PTP) epsilon. As such, cyt-PTP epsilon enables analysis of phosphatase regulation in the absence of extracellular domains, which participate in dimerization and inactivation of the receptor-type phosphatases re...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.15.5460-5471.2003

    authors: Toledano-Katchalski H,Tiran Z,Sines T,Shani G,Granot-Attas S,den Hertog J,Elson A

    更新日期:2003-08-01 00:00:00

  • Induction of Sp1 in differentiating human embryonal carcinoma cells triggers transcription of the fibronectin gene.

    abstract::Cells of the human embryonal carcinoma line NEC14 proliferate as densely packed clusters consisting of small, polygonal stem cells and do not express a detectable level of fibronectin (FN). Upon induction of differentiation by treatment with N,N'-hexamethylene bisacetamide (HMBA), the level of FN mRNA increased steepl...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.5.3010

    authors: Suzuki M,Oda E,Nakajima T,Sekiya S,Oda K

    更新日期:1998-05-01 00:00:00

  • A human globin enhancer causes both discrete and widespread alterations in chromatin structure.

    abstract::Gene activation requires alteration of chromatin structure to facilitate active transcription complex formation at a gene promoter. Nucleosome remodeling complexes and histone modifying complexes each play unique and interdependent roles in bringing about these changes. The role of distant enhancers in these structura...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.22.8099-8109.2003

    authors: Kim A,Dean A

    更新日期:2003-11-01 00:00:00

  • Replication in hydroxyurea: it's a matter of time.

    abstract::Hydroxyurea (HU) is a DNA replication inhibitor that negatively affects both the elongation and initiation phases of replication and triggers the "intra-S phase checkpoint." Previous work with budding yeast has shown that, during a short exposure to HU, MEC1/RAD53 prevent initiation at some late S phase origins. In th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00719-07

    authors: Alvino GM,Collingwood D,Murphy JM,Delrow J,Brewer BJ,Raghuraman MK

    更新日期:2007-09-01 00:00:00

  • c-Myc is necessary for DNA damage-induced apoptosis in the G(2) phase of the cell cycle.

    abstract::The c-myc proto-oncogene encodes a transcription factor that participates in the regulation of cellular proliferation, differentiation, and apoptosis. Ectopic overexpression of c-Myc has been shown to sensitize cells to apoptosis. We report here that cells lacking c-Myc activity due to disruption of the c-myc gene by ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.15.4929-4937.2001

    authors: Adachi S,Obaya AJ,Han Z,Ramos-Desimone N,Wyche JH,Sedivy JM

    更新日期:2001-08-01 00:00:00

  • Mouse Zac1, a transcriptional coactivator and repressor for nuclear receptors.

    abstract::Transcriptional activation by nuclear hormone receptors is mediated by the 160-kDa family of nuclear receptor coactivators. These coactivators associate with DNA-bound nuclear receptors and transmit activating signals to the transcription machinery through two activation domains. In screening for mammalian proteins th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.5.1855-1867.2000

    authors: Huang SM,Stallcup MR

    更新日期:2000-03-01 00:00:00

  • Dax-1 and steroid receptor RNA activator (SRA) function as transcriptional coactivators for steroidogenic factor 1 in steroidogenesis.

    abstract::The nuclear receptor steroidogenic factor 1 (SF-1) is essential for adrenal development and steroidogenesis. The atypical orphan nuclear receptor Dax-1 binds to SF-1 and represses SF-1 target genes. Paradoxically, however, loss-of-function mutations of Dax-1 also cause adrenal hypoplasia, suggesting that Dax-1 may fun...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01010-08

    authors: Xu B,Yang WH,Gerin I,Hu CD,Hammer GD,Koenig RJ

    更新日期:2009-04-01 00:00:00