2021
Selective deletion of the receptor for CSF1, c-fms, in osteoclasts results in a high bone mass phenotype, smaller osteoclasts in vivo and an impaired response to an anabolic PTH regimen
Zhu M, Sun BH, Nevius E, Kaplan J, Pereira J, Insogna K. Selective deletion of the receptor for CSF1, c-fms, in osteoclasts results in a high bone mass phenotype, smaller osteoclasts in vivo and an impaired response to an anabolic PTH regimen. PLOS ONE 2021, 16: e0247199. PMID: 33607650, PMCID: PMC7895546, DOI: 10.1371/journal.pone.0247199.Peer-Reviewed Original ResearchConceptsColony stimulating factor 1Mature osteoclastsBone massHigh bone mass phenotypeAttenuated anabolic responseDaily subcutaneous dosesTrabecular bone massBone mass phenotypeC-fmsNormal tooth eruptionTrabecular bone compartmentsMature osteoclast functionCathepsin K promoterFemurs of maleWild-type animalsOcS/BSFemale knockSubcutaneous dosesNormal weightSmall osteoclastsImpaired responseTrabecular numberAnabolic responseFlox miceMass phenotype
2006
Activated c-Fms recruits Vav and Rac during CSF-1-induced cytoskeletal remodeling and spreading in osteoclasts
Sakai H, Chen Y, Itokawa T, Yu KP, Zhu ML, Insogna K. Activated c-Fms recruits Vav and Rac during CSF-1-induced cytoskeletal remodeling and spreading in osteoclasts. Bone 2006, 39: 1290-1301. PMID: 16950670, DOI: 10.1016/j.bone.2006.06.012.Peer-Reviewed Original ResearchMeSH KeywordsActinsAndrostadienesAnimalsBiological Transport, ActiveCdc42 GTP-Binding ProteinCells, CulturedCytoskeletonEnzyme InhibitorsGuanosine TriphosphateHumansMacrophage Colony-Stimulating FactorMiceModels, BiologicalOsteoclastsPhosphoinositide-3 Kinase InhibitorsProtein BindingProto-Oncogene Proteins c-vavPseudopodiaRac GTP-Binding ProteinsRatsReceptor, Macrophage Colony-Stimulating FactorRecombinant ProteinsSignal TransductionWortmanninConceptsCSF-1GEF activityCytoskeletal remodelingGTPase activityAssociation of VavC-fmsRac GTPase activityDominant negative Cdc42Dominant-negative RacCSF-1 receptorInhibitors of PI3CSF-1 treatmentTarget GTPaseActive RacExchange factorActive Cdc42Actin reorganizationLamellipodia formationPhosphotyrosine contentC-SrcPlasma membraneInhibitor of RhoARapid translocationVavRac translocation
2004
The expanding role of PI3-kinase in bone
Golden LH, Insogna KL. The expanding role of PI3-kinase in bone. Bone 2004, 34: 3-12. PMID: 14751558, DOI: 10.1016/j.bone.2003.09.005.BooksConceptsRole of PI3PI3-KsC-fmsTyrosine kinase c-SrcKinase c-SrcDifferent substrate specificitiesCritical downstream effectorCell surface receptorsActin remodelingSignal transductionPI3-kinaseC-SrcSubstrate specificityDownstream effectorsOsteoblast differentiationCellular responsesPI3Attachment structuresEffector actionOsteoclast survivalRegulationRecent evidenceImportant roleTransductionRole
1997
Colony-stimulating factor-1 induces cytoskeletal reorganization and c-src-dependent tyrosine phosphorylation of selected cellular proteins in rodent osteoclasts.
Insogna KL, Sahni M, Grey AB, Tanaka S, Horne WC, Neff L, Mitnick M, Levy JB, Baron R. Colony-stimulating factor-1 induces cytoskeletal reorganization and c-src-dependent tyrosine phosphorylation of selected cellular proteins in rodent osteoclasts. Journal Of Clinical Investigation 1997, 100: 2476-2485. PMID: 9366562, PMCID: PMC508448, DOI: 10.1172/jci119790.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnimals, NewbornCell MovementCells, CulturedCytoskeletonKineticsMacrophage Colony-Stimulating FactorMolecular Sequence DataOsteoclastsPeptidesPhosphoproteinsPhosphorylationPhosphotyrosinePolymerase Chain ReactionProto-Oncogene Proteins pp60(c-src)RatsSrc-Family KinasesSubstrate SpecificityConceptsColony-stimulating factor-1CSF-1 treatmentC-SrcC-fmsCellular proteinsC-Src-dependent tyrosine phosphorylationGrb2-binding proteinSrc kinase activityFactor 1Normal cytoskeletal architectureCytoskeletal architectureSrc geneCytoskeletal reorganizationTyrosine phosphorylationKinase activityPhosphotyrosine stainingCellular eventsF-actinActin distributionTargeted disruptionProteinRapid cytoplasmicLike cellsPhosphorylationOsteoclast-like cellsRole of c‐Src in cellular events associated with colony‐stimulating factor‐1‐induced spreading in osteoclasts
Insogna K, Tanaka S, Neff L, Horne W, Levy J, Baron R. Role of c‐Src in cellular events associated with colony‐stimulating factor‐1‐induced spreading in osteoclasts. Molecular Reproduction And Development 1997, 46: 104-108. PMID: 8981371, DOI: 10.1002/(sici)1098-2795(199701)46:1<104::aid-mrd16>3.0.co;2-2.BooksMeSH KeywordsActininAnimalsBone MarrowBone Marrow CellsCalcitriolCell SizeCells, CulturedCytoskeletonFemaleHumansMacrophage Colony-Stimulating FactorMiceMicroscopy, ConfocalOsteoblastsOsteoclastsOsteoporosisPhosphatidylinositol 4,5-DiphosphatePhosphorylationProtein Processing, Post-TranslationalProto-Oncogene Proteins pp60(c-src)RatsSignal TransductionConceptsOsteoclast-like cellsNeonatal rat osteoclastsRat osteoclastsCSF-1 treatmentMonoclonal antibodiesC-fmsCSF-1C-SrcCellular eventsWestern blot analysisTime-dependent increaseMurine bone marrowBasal abnormalitiesBone marrowConfocal microscopic studiesPIP2 contentSignificant doseReceptor tyrosine kinasesOsteoclastsTyrosine kinase activityC-Src kinase activityCell-signaling eventsTargeted disruptionTreatmentIntrinsic tyrosine kinase activity