Affinage

CSF1

Macrophage colony-stimulating factor 1 · UniProt P09603

Length
554 aa
Mass
60.2 kDa
Annotated
2026-06-09
100 papers in source corpus 24 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CSF1 (M-CSF) is a stromal-derived cytokine that drives the survival, proliferation, differentiation, and lineage commitment of myeloid cells by activating its receptor tyrosine kinase CSF-1R (c-Fms) (PMID:23575636, PMID:16294221). Receptor activation is gated by an ubiquitin-dependent amplification loop: CSF-1R phospho-Tyr-559 recruits Src family kinases, and c-Cbl-mediated, E3-ligase-dependent receptor ubiquitination drives a kinase-domain conformational change required for full receptor tyrosine phosphorylation, while the same Cbl-coordinated multiubiquitination also triggers receptor internalization and degradation to attenuate signaling (PMID:10393178, PMID:21041311). The activated receptor branches into PI3K/Akt/mTOR-S6K signaling that sustains cell survival and translation (PMID:14502240), a PLCgamma2/ERK arm that stabilizes c-Fos and phosphorylates C/EBPalpha to specify monocyte commitment (PMID:19587381), and a PI3K→PLC→DAG→PKC/Ras cascade and Rac-dependent actin remodeling that govern macropinocytosis and cytoskeletal reorganization (PMID:25688212). A distinct CSF-1R autophosphorylation site, Y807, acts as a switch between proliferation and differentiation (PMID:8981370). In the nucleus, M-CSF/MAPK signaling phosphorylates Mitf/TFE3 to recruit p300 and enable osteoclast maturation (PMID:11684011), and at the level of stem cells M-CSF directly induces the master regulator PU.1 to instruct myeloid fate in single hematopoietic stem cells (PMID:23575636). CSF1 is produced as secreted, proteoglycan, and cell-surface forms by diverse stromal sources — bone marrow Adipoq-lineage progenitors, lymphatic and other endothelial cells, mesothelial cells, and intimal smooth muscle cells — to sustain tissue-resident macrophage and osteoclast populations in a paracrine manner (PMID:11418465, PMID:36779851, PMID:36779854, PMID:28052488), and it is a central effector in pathological bone resorption, linking TNF-alpha and estrogen-deficiency signals to osteoclastogenesis (PMID:16294221, PMID:10792003). Beyond myeloid biology, CSF-1R supports Paneth cell maturation and the intestinal stem cell niche (PMID:23314290) and promotes neuronal survival and function during brain development (PMID:8787741).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1992 Medium

    Established that CSF1 acts through c-Fms beyond classical myeloid targets, showing pathologically altered cells can acquire receptor responsiveness.

    Evidence c-fms expression, M-CSF binding, phosphotyrosine immunoblot and proliferation assays in arteriosclerotic intimal smooth muscle cells

    PMID:1531986

    Open questions at the time
    • Did not define downstream signaling branches engaged in smooth muscle cells
    • Mechanism of ectopic c-fms induction unresolved
  2. 1996 Medium

    Extended CSF1 function into the nervous system, demonstrating a non-myeloid trophic role in vivo.

    Evidence Neuronal culture survival/outgrowth assays, expression analysis, evoked-potential electrophysiology, and CSF-1 rescue injection in op/op mice

    PMID:8787741

    Open questions at the time
    • Direct vs. microglia-mediated neuronal effect not separated
    • Receptor-bearing cell type mediating rescue not defined
  3. 1997 Medium

    Mapped the growth-versus-differentiation decision to a specific receptor autophosphorylation site, defining a molecular switch.

    Evidence Site-directed mutagenesis of CSF-1R tyrosines in FDC-P1 cells with differentiation/proliferation readouts

    PMID:8981370

    Open questions at the time
    • Effector bound at Y807 not identified
    • Single cell-line context
  4. 1999 High

    Identified Cbl as the coordinator of CSF-1R ubiquitination and endocytosis, defining the negative-feedback arm of signaling.

    Evidence Cbl-/- macrophages, reciprocal Co-IP, ubiquitination and receptor internalization assays

    PMID:10393178

    Open questions at the time
    • Did not yet show ubiquitination is required for receptor activation (later refined)
    • Specific lysines ubiquitinated not mapped
  5. 2000 High

    Placed CSF1 epistatically downstream of estrogen-deficiency signaling in bone loss, establishing it as a required mediator of osteoclastogenesis.

    Evidence In vivo M-CSF neutralizing antibody and Egr-1 knockout mice in an ovariectomy model with bone resorption/mass readouts

    PMID:10792003

    Open questions at the time
    • Stromal cell type producing M-CSF not defined
    • Direct Egr-1 binding to the Csf1 promoter not shown
  6. 2001 High

    Defined a nuclear endpoint of M-CSF/MAPK signaling required for osteoclast maturation.

    Evidence Phosphorylation assays, p300 Co-IP, mutagenesis of a MAPK serine, and differentiation assays in Mitf(mi/mi) osteoclasts

    PMID:11684011

    Open questions at the time
    • Direct kinase phosphorylating Mitf/TFE3 not identified
    • Target genes driven by p300 recruitment not enumerated
  7. 2001 High

    Defined the molecular forms and tissue sources of CSF1 and proved the membrane-spanning precursor is sufficient to rescue the null phenotype.

    Evidence Transgenic rescue of Csf1(op)/op mice with a precursor transgene plus lacZ reporter and tissue protein measurements

    PMID:11418465

    Open questions at the time
    • Relative functional contributions of secreted vs. membrane forms not dissected
    • Cell-autonomous requirement at each new site not tested
  8. 2002 Low

    Outlined the Fms→PI3K/PLCgamma→Rac→actin axis governing microglial cytoskeletal responses.

    Evidence Signaling/pathway analysis in microglia (review-style with experimental basis)

    PMID:12379904

    Open questions at the time
    • Review-style abstract with limited methodological detail
    • Iba1 role in the pathway not mechanistically resolved
  9. 2003 Medium

    Mapped M-CSF survival signaling to convergent mTOR/S6K-dependent translation control in osteoclasts.

    Evidence Pharmacological inhibition of PI3K/Akt/ERK/mTOR with apoptosis and bone resorption assays

    PMID:14502240

    Open questions at the time
    • Inhibitor-based dissection without genetic confirmation
    • Convergence point of M-CSF, TNF, RANKL not molecularly defined
  10. 2003 Medium

    Established that M-CSF instructs macrophages to secrete biologically active VEGF, linking the cytokine to angiogenesis.

    Evidence Human monocyte culture, VEGF ELISA, HUVEC tube formation, and anti-VEGF neutralization

    PMID:12928417

    Open questions at the time
    • Signaling pathway from CSF-1R to VEGF induction not defined
    • In vivo relevance not tested
  11. 2004 Medium

    Revealed a viral subversion mechanism in which HIV-1 Nef-activated Hck hijacks the M-CSF receptor complex to blunt signaling.

    Evidence Conditional Nef in TF-1-fms cells, Co-IP, receptor phosphorylation, and proliferation/differentiation assays

    PMID:15626739

    Open questions at the time
    • Mechanism of Hck-mediated receptor inhibition not defined
    • Single cell-line model
  12. 2005 High

    Positioned M-CSF in the inflammatory osteoclastogenesis cascade between TNF-alpha and RANK induction, and validated receptor blockade therapeutically.

    Evidence TNF-receptor chimeric bone marrow mice, anti-c-Fms blocking antibody, and TRACP 5b resorption marker in arthritis/TNF models

    PMID:16294221

    Open questions at the time
    • Transcriptional mechanism of M-CSF-induced RANK expression not defined
  13. 2005 Medium

    Showed CSF1 represses OPG to permit osteoclastogenesis required for tooth eruption, defining a transcriptional regulatory output.

    Evidence CSF-1-deficient tl/tl rats and siRNA knockdown in dental follicle cells with OPG expression readout

    PMID:16109994

    Open questions at the time
    • Direct vs. indirect OPG regulation not distinguished
    • Signaling intermediate to OPG promoter unknown
  14. 2006 Medium

    Demonstrated physical and functional coupling of c-Fms with alphaVbeta3 integrin and an adhesion signaling complex in osteoclasts.

    Evidence Anion-exchange chromatography, sequential immunoprecipitation, and co-localization microscopy in osteoclasts

    PMID:16600665

    Open questions at the time
    • Functional consequence of cFms-alphaVbeta3 association not directly perturbed
    • Timing relative to phosphorylation peak unexplained
  15. 2009 Medium

    Defined the PLCgamma2/ERK→c-Fos/C/EBPalpha pathway by which M-CSF specifies monocyte lineage in progenitors.

    Evidence Ba/F3-fms and lineage-negative marrow cells with ERK/PLC inhibitors and colony assays

    PMID:19587381

    Open questions at the time
    • Inhibitor-based, no genetic confirmation in primary HSPCs
    • Direct C/EBPalpha-c-Fos interaction not shown
  16. 2010 High

    Refined the role of ubiquitination, showing c-Cbl-dependent CSF-1R ubiquitination is required for full kinase activation, not just receptor downregulation.

    Evidence CSF-1R mutagenesis (Y559), c-Cbl-deficient macrophages reconstituted with WT vs. ligase-dead C381A Cbl, and SFK inhibitors

    PMID:21041311

    Open questions at the time
    • Structural basis of the proposed kinase-domain conformational change not resolved
    • Ubiquitin chain topology not defined
  17. 2010 Medium

    Distinguished CSF1 from the alternative c-Fms ligand IL-34, showing distinct receptor binding sites and signaling kinetics.

    Evidence Receptor binding competition with distinct blocking MAbs, phosphorylation kinetics, and functional growth/migration assays

    PMID:20489731

    Open questions at the time
    • Structural footprints of each ligand on Fms not mapped
    • Physiological division of labor between ligands not addressed
  18. 2012 Medium

    Extended CSF-1R function to the intestinal epithelium, showing it supports Paneth cells and the stem cell niche cell-intrinsically.

    Evidence GI-specific Csf1r knockout, intestinal organoid culture, and stem cell marker immunohistochemistry

    PMID:23314290

    Open questions at the time
    • Source of the CSF-1R ligand in this niche not defined
    • Downstream signaling in Paneth cells not characterized
  19. 2013 High

    Demonstrated that M-CSF directly instructs myeloid cell fate in single HSCs via PU.1 induction, independent of survival/proliferation selection.

    Evidence Single-cell video imaging, single-cell gene expression, PU.1 reporter, and in vivo M-CSF administration with receptor-deficient controls

    PMID:23575636

    Open questions at the time
    • Signaling intermediates from CSF-1R to PU.1 transcription not mapped
    • Chromatin mechanism of PU.1 induction unknown
  20. 2015 Medium

    Resolved the lipid-signaling sequence underlying M-CSF-induced macropinocytosis in macrophages.

    Evidence Live-cell fluorescent lipid probes with PI3K/PLC/PKC/Ras/Akt inhibitors and macropinocytosis quantification

    PMID:25688212

    Open questions at the time
    • Effectors linking DAG/PKC/Ras to actin cup closure not identified
    • Pharmacology-only dissection
  21. 2017 Medium

    Identified lymphatic endothelial cells as an M-CSF source capable of driving pathological osteolysis.

    Evidence LEC-osteoclast co-culture, M-CSF neutralization, Ki20227 inhibition, and intra-tibial LEC injection with micro-CT/ELISA

    PMID:28052488

    Open questions at the time
    • Physiological vs. pathological contribution of LEC-derived M-CSF unclear
    • Single lab
  22. 2019 Low

    Implicated mesothelial cells as a paracrine M-CSF source sustaining peritoneal macrophages.

    Evidence Detection of membrane-bound and secreted CSF1 in mesothelial cells with peritoneal macrophage proximity analysis

    PMID:31251389

    Open questions at the time
    • Limited methodological detail establishing functional dependence
    • No genetic source-specific deletion
  23. 2023 High

    Pinpointed bone marrow Adipoq-lineage progenitors as a dominant physiological source of M-CSF for marrow macrophages and osteoclasts.

    Evidence Adipoq-Cre conditional Csf1 deletion with bone histology, TRAP, flow cytometry, and ovariectomy model; replicated across two studies

    PMID:36779851 PMID:36779854

    Open questions at the time
    • Relative contribution versus other stromal sources not fully quantified
    • Regulation of CSF1 expression in these progenitors not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CSF-1R signaling output is selectively wired to distinct fates (proliferation vs. differentiation vs. PU.1-driven commitment) across cell types, and the structural basis of ubiquitination-driven kinase activation, remain unresolved.
  • No structure of the ubiquitination-induced active CSF-1R conformation
  • Signaling intermediates from CSF-1R to PU.1 not mapped
  • Quantitative source hierarchy of CSF1 across tissues incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005576 extracellular region 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 3
Partners
BCAR1CBLCSF1RHCKIL34ITGB3PTK2B
Complex memberships
cFms-alphaVbeta3 integrin complex (with Pyk2, p130Cas, c-Cbl)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 CSF-1 activation of CSF-1R causes Cbl tyrosine phosphorylation, Cbl-CSF-1R association, and their simultaneous multiubiquitination at the plasma membrane, leading to rapid CSF-1R internalization and degradation. Cbl-/- macrophages fail to exhibit CSF-1R multiubiquitination and show slower CSF-1R internalization, demonstrating that Cbl positively regulates coordinated CSF-1R multiubiquitination and endocytosis to attenuate proliferative signaling. Gene-targeted knockout macrophages (Cbl-/-), Co-immunoprecipitation, ubiquitination assay, receptor internalization assay The EMBO journal High 10393178
2010 CSF-1R phospho-Tyr-559 is required for binding of Src family kinases (SFKs), and this site is both necessary and sufficient for CSF-1-induced CSF-1R ubiquitination and tyrosine phosphorylation. c-Cbl-mediated CSF-1R ubiquitination (dependent on its E3 ligase activity) is required for a conformational change in the kinase domain enabling amplification of receptor tyrosine phosphorylation and full receptor activation. Site-directed mutagenesis of CSF-1R, c-Cbl-deficient macrophages, reconstitution with wild-type vs. ubiquitin ligase-dead C381A c-Cbl, SFK inhibitors The Journal of biological chemistry High 21041311
2001 M-CSF induces phosphorylation of transcription factors Mitf and TFE3 via a conserved MAPK consensus site, triggering recruitment of the coactivator p300. An unphosphorylatable mutant at this MAPK serine specifically fails to support formation of multinucleated osteoclasts, linking M-CSF/MAPK signaling to Mitf/TFE3 phosphorylation as a nuclear target required for osteoclast maturation. Phosphorylation assay, co-immunoprecipitation with p300, site-directed mutagenesis, cell differentiation assay in Mitf(mi/mi) osteoclasts Molecular cell High 11684011
2013 M-CSF directly induces expression of the myeloid master regulator PU.1 in single hematopoietic stem cells (HSCs) and instructs myeloid cell-fate change independently of selective survival or proliferation. In vivo, high systemic M-CSF drives M-CSF-receptor-dependent activation of endogenous PU.1 protein in single HSCs, causing a PU.1-dependent myeloid differentiation preference. Single-cell video imaging, single-cell gene expression analysis, PU.1 promoter reporter assay, in vivo M-CSF administration in mice, M-CSF receptor-deficient controls Nature High 23575636
2003 M-CSF, TNF-alpha, and RANKL promote osteoclast survival through convergent signaling on mTOR/S6 kinase. M-CSF signals to Akt, and inhibition of PI3K, Akt, ERKs, geranylgeranylated proteins, or mTOR/S6K induces osteoclast apoptosis. mTOR regulates protein translation via S6K, 4E-BP1, and S6, and inhibition of translation by other mechanisms also induces osteoclast apoptosis. Pharmacological inhibition (rapamycin, PI3K inhibitors, ERK inhibitors), S6K phosphorylation assay, apoptosis assay, in vitro bone resorption assay Cell death and differentiation Medium 14502240
2005 TNF-alpha stimulates M-CSF gene expression in stromal cells via TNF-responsive stromal cells, and M-CSF in turn induces RANK expression in osteoclast precursors. Antibody blockade of the M-CSF receptor c-Fms selectively and completely arrested pathological osteoclastogenesis and bone resorption in inflammatory arthritis and TNF-injected mice. Chimeric bone marrow transplant mice (TNF receptor-deficient stromal vs. precursor cells), anti-c-Fms blocking antibody in vivo, TRACP 5b bone resorption marker measurement The Journal of clinical investigation High 16294221
2000 M-CSF neutralization in vivo completely prevents the rise in osteoclast number, increase in bone resorption, and bone loss induced by ovariectomy. Estrogen deficiency induces M-CSF production through an Egr-1-dependent mechanism; Egr-1-deficient mice with maximally stimulated stromal M-CSF production show increased bone resorption reversed by anti-M-CSF antibody. In vivo M-CSF neutralizing antibody, ovariectomy model, Egr-1 knockout mice, bone resorption and mass measurements The Journal of clinical investigation High 10792003
2009 M-CSF preferentially activates PLCgamma2 and thereby ERK to stabilize c-Fos and stimulate C/EBPalpha(S21) phosphorylation in myeloid progenitors, favoring monocyte lineage commitment. ERK inhibition prevented M-CSF-induced c-Fos induction, reduced C/EBPalpha phosphorylation, and decreased colony-forming unit-monocytes, establishing a mechanistic pathway from M-CSF receptor to monocyte specification. Receptor-expressing Ba/F3 cells, lineage-negative murine marrow cells, ERK inhibitors, PLC inhibitors, colony assays Blood Medium 19587381
1997 CSF-1R autophosphorylation site Y807 is essential for the differentiation signal: its mutation completely abrogates differentiation and conversely increases M-CSF-dependent proliferation, suggesting Y807 controls a switch between growth and differentiation. Sites Y697, Y706, and Y721 in the kinase insert region augment but are not required for differentiation. Site-directed mutagenesis of CSF-1R tyrosine sites, expression in FDC-P1 myeloid cells, differentiation and proliferation assays Molecular reproduction and development Medium 8981370
2015 M-CSF-induced macropinocytosis in macrophages proceeds through a sequential PI3K → PLC → DAG → PKC/Ras pathway. PIP3 (PI3K product) appears in cups prior to DAG; PLC inhibitor blocks M-CSF-induced but not PMA-induced macropinocytosis; Ras and PKC inhibitors block both. Akt inhibition does not block macropinocytosis despite Akt activation by M-CSF. Live-cell fluorescent lipid probes, pharmacological inhibitors (PI3K, PLC, PKC, Ras, Akt), macropinocytosis quantification Frontiers in physiology Medium 25688212
2010 IL-34 and M-CSF share the Fms receptor but differ in receptor binding domains, signal activation kinetics, and downstream biological activities. IL-34 induces stronger but more transient tyrosine phosphorylation of Fms and downstream molecules and more rapidly downregulates Fms. An anti-Fms MAb blocked both IL-34-Fms and M-CSF-Fms binding, but another MAb blocked only M-CSF-Fms binding, indicating distinct binding sites on Fms. Receptor binding competition assay with blocking MAbs, phosphorylation kinetics assay, cell growth/survival assay, migration assay, morphological analysis Cell death and differentiation Medium 20489731
2006 M-CSF induces stable association of the M-CSF receptor cFms with alphaVbeta3 integrin in osteoclasts. The cFms-alphaVbeta3 complex also contains Pyk2, p130Cas, and c-Cbl. Association is induced by M-CSF but peaks after the peak of cFms tyrosine phosphorylation. Co-localization of both receptors occurs in the podosomal actin ring during adhesion on glass but not in the sealing zone on bone. Anion-exchange chromatography, sequential immunoprecipitation, co-localization by microscopy in osteoclasts The international journal of biochemistry & cell biology Medium 16600665
2004 HIV-1 Nef interferes with the M-CSF/M-CSF receptor signaling pathway through Hck activation. Nef-activated Hck constitutively associates with the M-CSF receptor complex, causing markedly diminished tyrosine phosphorylation/activation of the M-CSF receptor in response to M-CSF and consequent inhibition of M-CSF-mediated proliferation and macrophage differentiation. Conditionally active Nef construct in TF-1-fms myeloid cells, receptor tyrosine phosphorylation assay, co-immunoprecipitation, proliferation and differentiation assays Blood Medium 15626739
2001 CSF-1 is expressed as a secreted glycoprotein, proteoglycan (circulating or matrix-bound), or biologically active cell-surface glycoprotein. A 3.13-kb CSF-1 promoter/first intron driving the membrane-spanning CSF-1 precursor transgene rescues all gross phenotypic defects of Csf1-null op/op mice, identifying new cellular sites of CSF-1 expression including ovarian granulosa cells, mammary ductal epithelium, testicular Leydig cells, serous acinar cells, and Paneth cells. Transgenic rescue of Csf1(op)/Csf1(op) null mice, lacZ reporter under same promoter, tissue CSF-1 protein measurements, hematopoietic parameter analysis Blood High 11418465
2003 M-CSF induces VEGF production and release from human monocytes in a dose-dependent manner. VEGF released by M-CSF-stimulated monocytes is biologically active as it induces tube formation in HUVECs, an effect blocked by anti-VEGF antibody. Human monocyte culture with recombinant M-CSF, VEGF ELISA, HUVEC tube formation assay, antibody neutralization Journal of immunology Medium 12928417
2023 Bone marrow Adipoq-lineage progenitors (but not mature adipocytes) are a major cellular source of M-CSF in bone marrow, expressing CSF1 at much higher levels than osteoblast lineage cells. Cell-specific deletion of Csf1 in Adipoq-lineage progenitors drastically reduces bone marrow macrophage and osteoclast generation, causing severe osteopetrosis, and significantly alleviates ovariectomy-induced osteoporosis. Cell-specific conditional knockout (Adipoq-Cre), bone histology, TRAP staining, flow cytometry, bone mass measurement, ovariectomy model eLife High 36779851 36779854
2017 Lymphatic endothelial cells (LECs) produce high levels of M-CSF (but not RANKL, IL-6, or TNF), and LEC-mediated osteoclast formation and bone resorption are blocked by an M-CSF neutralizing antibody or M-CSF receptor inhibitor Ki20227. Intra-tibial LEC injection in mice causes massive osteolysis with elevated serum and bone marrow M-CSF, reversed by Ki20227 treatment. LEC-osteoclast co-culture, M-CSF neutralizing antibody, Ki20227 pharmacological inhibition, intra-tibial LEC injection mouse model, micro-CT, ELISA Journal of bone and mineral research Medium 28052488
2012 CSF-1R (expressed primarily on Paneth cells) directly supports Paneth cell maturation and thereby fashions the intestinal stem cell niche. GI-specific Csf1r deletion in young adult mice leads to Paneth cell loss, changed distribution of proliferating cells, and loss of Lgr5 and other stem cell marker expression. Csf1r-/- crypts in organoid culture show the Paneth cell defect is epithelial cell-intrinsic and affects stem cell activity. Conditional Csf1r knockout (GI-specific), intestinal organoid culture, immunohistochemistry for stem cell markers, 3D localization of CSF-1R Stem cell research Medium 23314290
1996 CSF-1 promotes neuronal survival and process outgrowth in vitro in a dose-dependent manner. Both CSF-1 and its receptor are expressed in developing mouse brain. CSF-1-null op/op mice exhibit abnormal brainstem auditory and visual evoked potentials and aberrant cortical neuronal function; daily CSF-1 injection of postnatal op/op mice largely rescues these neurological abnormalities. Neuronal culture with CSF-1 treatment, nuclease protection assay for CSF-1/receptor expression, electrophysiological assays (evoked potentials, intracortical recordings), in vivo CSF-1 rescue injections in op/op mice Development Medium 8787741
2019 Mesothelial cells produce both membrane-bound and secreted CSF1 that sustain peritoneal macrophage proliferation and growth. Peritoneal macrophages are found in close proximity to mesothelial cells in the peritoneal cavity. CSF1 protein detection in mesothelial cells (membrane and secreted forms), peritoneal macrophage localization, co-culture/proximity analysis European journal of immunology Low 31251389
2005 CSF-1 down-regulates OPG gene expression in dental follicle cells in vivo, enabling osteoclastogenesis required for tooth eruption. CSF-1-deficient toothless (tl/tl) rats show higher OPG expression in dental follicle than normal littermates; siRNA knockdown of CSF-1 mRNA in dental follicle cells causes OPG upregulation. Comparison of OPG expression in CSF-1-deficient vs. normal rats, siRNA knockdown of CSF-1 in dental follicle cells, OPG gene expression analysis Journal of dental research Medium 16109994
2002 M-CSF activates Fms tyrosine kinase, which sequentially activates PI3K or PLCgamma, leading to activation of the small GTPase Rac, which regulates actin cytoskeletal reorganization in microglia. Iba1 (a macrophage/microglia-specific calcium-binding protein) is involved in the Rac signaling pathway downstream of M-CSF/PLCgamma. Intracellular signaling analysis in microglia, pathway inhibition/activation studies (described as review with experimental basis) Glia Low 12379904
1992 Smooth muscle cells from arteriosclerotic lesions express the M-CSF receptor c-fms and exhibit high-affinity M-CSF binding, unlike normal medial smooth muscle cells. M-CSF stimulation of these intimal smooth muscle cells causes tyrosine phosphorylation and increased cell proliferation. c-fms expression analysis, M-CSF binding assay, anti-phosphotyrosine immunoblot, cell proliferation assay, immunocytochemistry The Journal of biological chemistry Medium 1531986

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 CSF-1 receptor signaling in myeloid cells. Cold Spring Harbor perspectives in biology 664 24890514
2004 CSF-1 regulation of the wandering macrophage: complexity in action. Trends in cell biology 644 15519852
2016 Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage. Journal of leukocyte biology 441 27354413
2002 Intracellular signaling in M-CSF-induced microglia activation: role of Iba1. Glia 302 12379904
2013 M-CSF instructs myeloid lineage fate in single haematopoietic stem cells. Nature 297 23575636
2003 M-CSF, TNFalpha and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase. Cell death and differentiation 296 14502240
1999 The Cbl protooncoprotein stimulates CSF-1 receptor multiubiquitination and endocytosis, and attenuates macrophage proliferation. The EMBO journal 253 10393178
1987 Expression of the M-CSF (CSF-1) gene by human monocytes. Blood 238 3105621
2005 M-CSF mediates TNF-induced inflammatory osteolysis. The Journal of clinical investigation 236 16294221
2015 M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment. Cancer research 201 26573801
2020 The M-CSF receptor in osteoclasts and beyond. Experimental & molecular medicine 192 32801364
2001 Rescue of the colony-stimulating factor 1 (CSF-1)-nullizygous mouse (Csf1(op)/Csf1(op)) phenotype with a CSF-1 transgene and identification of sites of local CSF-1 synthesis. Blood 183 11418465
2010 IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation. Cell death and differentiation 180 20489731
1997 CSF-1 signal transduction. Journal of leukocyte biology 173 9261328
2019 Function of CSF1 and IL34 in Macrophage Homeostasis, Inflammation, and Cancer. Frontiers in immunology 149 31552020
2007 Increased myeloid cell responses to M-CSF and RANKL cause bone loss and inflammation in SH3BP2 "cherubism" mice. Cell 149 17218256
2003 M-CSF induces vascular endothelial growth factor production and angiogenic activity from human monocytes. Journal of immunology (Baltimore, Md. : 1950) 141 12928417
1995 CSF-1 and its receptor in ovarian, endometrial and breast cancer. Annals of medicine 140 7742005
2006 M-CSF, c-Fms, and signaling in osteoclasts and their precursors. Annals of the New York Academy of Sciences 132 16831911
2001 Linkage of M-CSF signaling to Mitf, TFE3, and the osteoclast defect in Mitf(mi/mi) mice. Molecular cell 129 11684011
2021 The twin cytokines interleukin-34 and CSF-1: masterful conductors of macrophage homeostasis. Theranostics 115 33408768
1997 Elevated levels of M-CSF, sCD14 and IL8 in type 1 Gaucher disease. Blood cells, molecules & diseases 115 9236158
2013 IL-34 and CSF-1: similarities and differences. Journal of bone and mineral metabolism 112 23740288
2000 Early events in M-CSF receptor signaling. Growth factors (Chur, Switzerland) 111 10705574
2021 Functions of macrophage colony-stimulating factor (CSF1) in development, homeostasis, and tissue repair. Seminars in immunology 108 34742624
1996 CSF-1 deficiency in mice results in abnormal brain development. Development (Cambridge, England) 106 8787741
2001 Defective production of LIF, M-CSF and Th2-type cytokines by T cells at fetomaternal interface is associated with pregnancy loss. Journal of reproductive immunology 101 11600176
2012 Macrophage Migration and Its Regulation by CSF-1. International journal of cell biology 96 22505929
2015 Macrophage-colony stimulating factor (CSF1) predicts breast cancer progression and mortality. Anticancer research 92 25667468
2013 M-CSF increases proliferation and phagocytosis while modulating receptor and transcription factor expression in adult human microglia. Journal of neuroinflammation 92 23866312
2003 High dose M-CSF partially rescues the Dap12-/- osteoclast phenotype. Journal of cellular biochemistry 92 14624447
1989 Circulating levels of CSF-1 (M-CSF) a lymphohematopoietic cytokine may be a useful marker of disease status in patients with malignant ovarian neoplasms. International journal of radiation oncology, biology, physics 88 2663797
2007 M-CSF: a novel plasmacytoid and conventional dendritic cell poietin. Blood 87 17916748
2000 M-CSF neutralization and egr-1 deficiency prevent ovariectomy-induced bone loss. The Journal of clinical investigation 83 10792003
1997 Pressure regulates osteoclast formation and MCSF expression in marrow culture. Journal of cellular physiology 79 9012787
2021 M-CSF, IL-6, and TGF-β promote generation of a new subset of tissue repair macrophage for traumatic brain injury recovery. Science advances 78 33712456
2018 Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 77 29314558
2010 Antagonistic regulation of macrophage phenotype by M-CSF and GM-CSF: implication in atherosclerosis. Atherosclerosis 77 21159337
1998 M-CSF: haematopoietic growth factor or inflammatory cytokine? Cytokine 74 9505143
2012 M-CSF induces the expression of a membrane-bound form of IL-18 in a subset of human monocytes differentiating in vitro toward macrophages. European journal of immunology 73 22678914
2001 Local macrophage proliferation correlates with increased renal M-CSF expression in human glomerulonephritis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 73 11477167
1998 Biological activities and clinical application of M-CSF. International journal of hematology 71 9631577
2020 Lactic Acidosis Together with GM-CSF and M-CSF Induces Human Macrophages toward an Inflammatory Protumor Phenotype. Cancer immunology research 68 31924656
2014 Distinct role of FoxO1 in M-CSF- and GM-CSF-differentiated macrophages contributes LPS-mediated IL-10: implication in hyperglycemia. Journal of leukocyte biology 68 25420919
1992 Expression of M-CSF receptor encoded by c-fms on smooth muscle cells derived from arteriosclerotic lesion. The Journal of biological chemistry 67 1531986
1990 Differential expression of M-CSF, G-CSF, and GM-CSF by human monocytes. Journal of leukocyte biology 67 1689760
2020 Local M-CSF (Macrophage Colony-Stimulating Factor) Expression Regulates Macrophage Proliferation and Apoptosis in Atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 64 33086870
1991 Structure, biosynthesis and biological roles of monocyte-macrophage colony stimulating factor (CSF-1 or M-CSF). Nouvelle revue francaise d'hematologie 58 1838150
2014 CSF1 overexpression has pleiotropic effects on microglia in vivo. Glia 56 25042473
2013 M-CSF cooperating with NFκB induces macrophage transformation from M1 to M2 by upregulating c-Jun. Cancer biology & therapy 55 24100343
2009 M-CSF elevates c-Fos and phospho-C/EBPalpha(S21) via ERK whereas G-CSF stimulates SHP2 phosphorylation in marrow progenitors to contribute to myeloid lineage specification. Blood 55 19587381
2012 CSF-1 signaling in macrophages: pleiotrophy through phosphotyrosine-based signaling pathways. Critical reviews in clinical laboratory sciences 54 22468857
1997 Growth and differentiation signals regulated by the M-CSF receptor. Molecular reproduction and development 53 8981370
1991 Reassignment of the human CSF1 gene to chromosome 1p13-p21. Blood 52 1912583
2008 C-reactive protein induces M-CSF release and macrophage proliferation. Journal of leukocyte biology 50 19008293
2004 RANK, RANKL, OPG, and M-CSF expression in stromal cells during corneal wound healing. Investigative ophthalmology & visual science 50 15223796
1999 The role of CSF-1 in normal and neoplastic breast physiology. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) 48 9893162
2019 Distinctive Effects of GM-CSF and M-CSF on Proliferation and Polarization of Two Major Pulmonary Macrophage Populations. Journal of immunology (Baltimore, Md. : 1950) 46 30867240
2015 Differential signaling during macropinocytosis in response to M-CSF and PMA in macrophages. Frontiers in physiology 46 25688212
2005 CSF-1 regulation of osteoclastogenesis for tooth eruption. Journal of dental research 46 16109994
2023 Bone marrow Adipoq-lineage progenitors are a major cellular source of M-CSF that dominates bone marrow macrophage development, osteoclastogenesis, and bone mass. eLife 45 36779851
2003 Microglial overexpression of the M-CSF receptor augments phagocytosis of opsonized Abeta. Neurobiology of aging 44 12927763
1990 Steroid hormones induce macrophage colony-stimulating factor (MCSF) and MCSF receptor mRNAs in the human endometrium. Journal of molecular endocrinology 44 2147374
2010 A CSF-1 receptor phosphotyrosine 559 signaling pathway regulates receptor ubiquitination and tyrosine phosphorylation. The Journal of biological chemistry 42 21041311
2023 Nrf2 Mitigates RANKL and M-CSF Induced Osteoclast Differentiation via ROS-Dependent Mechanisms. Antioxidants (Basel, Switzerland) 40 38136214
2016 M-CSF improves protection against bacterial and fungal infections after hematopoietic stem/progenitor cell transplantation. The Journal of experimental medicine 40 27811055
2014 Increased expression of M-CSF and IL-13 in vitreous of patients with proliferative diabetic retinopathy: implications for M2 macrophage-involving fibrovascular membrane formation. The British journal of ophthalmology 40 25355804
2008 VEGF and M-CSF levels in periodontal tissue during tooth movement. Biomedical research (Tokyo, Japan) 39 18724005
2015 M-CSF priming of osteoclast precursors can cause osteoclastogenesis-insensitivity, which can be prevented and overcome on bone. Journal of cellular physiology 38 24962140
1989 The mononuclear phagocyte colony-stimulating factor (CSF-1, M-CSF). Hematology/oncology clinics of North America 38 2534393
2023 Csf1 from marrow adipogenic precursors is required for osteoclast formation and hematopoiesis in bone. eLife 37 36779854
2023 Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment. Cancer immunology, immunotherapy : CII 37 37505292
2006 Hepatocyte growth factor can substitute for M-CSF to support osteoclastogenesis. Biochemical and biophysical research communications 35 17022947
2005 CSF-1, RANKL and OPG regulate osteoclastogenesis during murine tooth eruption. Archives of oral biology 35 16137499
2018 M-CSF and IL-34 expression as indicators for growth in sporadic vestibular schwannoma. Virchows Archiv : an international journal of pathology 34 30580386
2014 Novel CSF1-S100A10 fusion gene and CSF1 transcript identified by RNA sequencing in tenosynovial giant cell tumors. International journal of oncology 34 24604026
2021 Withholding of M-CSF Supplement Reprograms Macrophages to M2-Like via Endogenous CSF-1 Activation. International journal of molecular sciences 33 33805444
2017 Lymphatic Endothelial Cells Produce M-CSF, Causing Massive Bone Loss in Mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 33 28052488
2011 CSF1 expression in nongynecological leiomyosarcoma is associated with increased tumor angiogenesis. The American journal of pathology 33 21854753
2002 Role of enhanced expression of m-CSF in conjunctiva affected by cicatricial pemphigoid. Investigative ophthalmology & visual science 33 12202518
2004 HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and inhibits M-CSF bioactivities. Blood 32 15626739
1996 M-CSF and GM-CSF promote alveolar macrophage differentiation into multinucleated giant cells with distinct phenotypes. Journal of leukocyte biology 32 8864136
2002 GM-CSF and M-CSF modulate beta-chemokine and HIV-1 expression in microglia. Glia 31 12112368
2019 Mesothelial cell CSF1 sustains peritoneal macrophage proliferation. European journal of immunology 28 31251389
2018 CSF-1 in Inflammatory and Arthritic Pain Development. Journal of immunology (Baltimore, Md. : 1950) 28 30120124
2008 The selective M-CSF receptor tyrosine kinase inhibitor Ki20227 suppresses experimental autoimmune encephalomyelitis. Journal of neuroimmunology 27 18378004
1997 Regulation of CSF-1 receptor expression. Molecular reproduction and development 27 8981363
2017 Beyond the M-CSF receptor - novel therapeutic targets in tumor-associated macrophages. The FEBS journal 26 28834216
2013 MicroRNA-Mediated Down-Regulation of M-CSF Receptor Contributes to Maturation of Mouse Monocyte-Derived Dendritic Cells. Frontiers in immunology 26 24198819
2011 Bisphosphonates modulate the expression of OPG and M-CSF in hMSC-derived osteoblasts. Clinical oral investigations 26 21938481
2022 Interactions in CSF1-Driven Tenosynovial Giant Cell Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 25 36007098
2020 Establishment of bone marrow-derived M-CSF receptor-dependent self-renewing macrophages. Cell death discovery 25 32714570
2012 The CSF-1 receptor fashions the intestinal stem cell niche. Stem cell research 25 23314290
2011 Feedback inhibition of osteoclastogenesis during inflammation by IL-10, M-CSF receptor shedding, and induction of IRF8. Annals of the New York Academy of Sciences 25 22082370
2011 M-CSF accelerates orthodontic tooth movement by targeting preosteoclasts in mice. The Angle orthodontist 24 21208080
1993 M-CSF gene transduction in multidrug-resistant human cancer cells to enhance anti-P-glycoprotein antibody-dependent macrophage-mediated cytotoxicity. International journal of cancer 23 8100809
2018 Concomitant type I IFN and M-CSF signaling reprograms monocyte differentiation and drives pro-tumoral arginase production. EBioMedicine 22 30528455
2014 M-CSF inhibits anti-HIV-1 activity of IL-32, but they enhance M2-like phenotypes of macrophages. Journal of immunology (Baltimore, Md. : 1950) 22 24748497
2006 M-CSF induces the stable interaction of cFms with alphaVbeta3 integrin in osteoclasts. The international journal of biochemistry & cell biology 22 16600665
1997 CSF-1 and cell cycle control in macrophages. Molecular reproduction and development 21 8981359

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