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
2019
Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X‐Linked Hypophosphatemia: A Phase 3, Single‐Arm, International Trial
Insogna KL, Rauch F, Kamenický P, Ito N, Kubota T, Nakamura A, Zhang L, Mealiffe M, San Martin J, Portale AA. Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X‐Linked Hypophosphatemia: A Phase 3, Single‐Arm, International Trial. Journal Of Bone And Mineral Research 2019, 34: 2183-2191. PMID: 31369697, PMCID: PMC6916280, DOI: 10.1002/jbmr.3843.Peer-Reviewed Original ResearchConceptsAdverse eventsWeek 48Fracture healingMore treatment-emergent adverse eventsTreatment-emergent adverse eventsProcedure-related adverse eventsOsteoid volume/bone volumeMost adverse eventsSerious adverse eventsTransiliac bone biopsiesSerum phosphorus concentrationPoor bone qualityRenal phosphate reabsorptionHuman monoclonal antibodyBone painPersistent osteomalaciaSubcutaneous burosumabPrimary endpointSkeletal complicationsAtraumatic fracturesChronic hypophosphatemiaSerum phosphorusDihydroxyvitamin DBone turnoverBone biopsy
2018
The contribution of cross-talk between the cell-surface proteins CD36 and CD47–TSP-1 in osteoclast formation and function
Koduru SV, Sun BH, Walker JM, Zhu M, Simpson C, Dhodapkar M, Insogna KL. The contribution of cross-talk between the cell-surface proteins CD36 and CD47–TSP-1 in osteoclast formation and function. Journal Of Biological Chemistry 2018, 293: 15055-15069. PMID: 30082316, PMCID: PMC6166722, DOI: 10.1074/jbc.ra117.000633.Peer-Reviewed Original ResearchConceptsOsteoclast formationTSP-1Competitive NO synthase inhibitorPro-osteoclastogenic effectAntibody-mediated blockadeNitroarginine methyl esterNO synthase inhibitorNitric Oxide SignalingPTH infusionDifferentiation 47Parathyroid hormoneBone resorptionFemale miceHypercalcemic responseOsteoclast maturationSynthase inhibitorResorptive activitySynthetic agonistsCD36Osteoclast progenitorsMiceInhibitory effectCD47OsteoclastsWT osteoblasts
2011
Control of bone formation by the serpentine receptor Frizzled-9
Albers J, Schulze J, Beil FT, Gebauer M, Baranowsky A, Keller J, Marshall RP, Wintges K, Friedrich FW, Priemel M, Schilling AF, Rueger JM, Cornils K, Fehse B, Streichert T, Sauter G, Jakob F, Insogna KL, Pober B, Knobeloch KP, Francke U, Amling M, Schinke T. Control of bone formation by the serpentine receptor Frizzled-9. Journal Of Cell Biology 2011, 192: 1057-1072. PMID: 21402791, PMCID: PMC3063134, DOI: 10.1083/jcb.201008012.Peer-Reviewed Original ResearchConceptsBone formationLow bone massBone loss disordersPotential downstream mediatorsBone massUbiquitin-like modifier ISG15Interferon-regulated genesTherapeutic implicationsLoss disordersCanonical Wnt signalingBone remodelingFrizzled 9Reduced expressionDownstream mediatorDifferentiation markersWnt signalingWnt receptorsNormal expressionPrimary osteoblastsFZD9OsteoblastsOsteoblast differentiationMatrix mineralizationMolecular analysisChemokines
2009
Where Wnts Went: The Exploding Field of Lrp5 and Lrp6 Signaling in Bone*
Williams BO, Insogna KL. Where Wnts Went: The Exploding Field of Lrp5 and Lrp6 Signaling in Bone*. Journal Of Bone And Mineral Research 2009, 24: 171-178. PMID: 19072724, PMCID: PMC3276354, DOI: 10.1359/jbmr.081235.BooksConceptsEffects of WntWnt pathwayBone metabolismDuodenal enterochromaffin cellsBone anabolic agentAction of WntNoncanonical signaling pathwaysRegulation of sclerostinDownstream effector moleculesEndogenous Wnt inhibitorsBone cell metabolismImportant regulatory moleculesAnabolic actionEnterochromaffin cellsSmall molecule inhibitorsSerotonin synthesisDrug discoveryTrophic stimuliNew therapiesBone anabolismAnabolic agentsTherapeutic targetEndocrine fashionFinal pathwayCentral regulator
2008
Lrp5 Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum
Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G. Lrp5 Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum. Cell 2008, 135: 825-837. PMID: 19041748, PMCID: PMC2614332, DOI: 10.1016/j.cell.2008.09.059.Peer-Reviewed Original ResearchConceptsBone massBone formationLrp5-deficient miceSerotonin blood levelsExpression of TPH1High bone massOsteoblast-specific disruptionRate-limiting biosynthetic enzymeBone lossEnterochromaffin cellsBlood levelsSerotonin synthesisPotential therapyBone remodelingWnt coreceptorSerotoninLRP5Function mutationsDuodenumTPH1Independent mannerOsteoporosisTherapyBiosynthetic enzymesMice
2004
The Impact of Dietary Protein on Calcium Absorption and Kinetic Measures of Bone Turnover in Women
Kerstetter JE, O’Brien K, Caseria DM, Wall DE, Insogna KL. The Impact of Dietary Protein on Calcium Absorption and Kinetic Measures of Bone Turnover in Women. The Journal Of Clinical Endocrinology & Metabolism 2004, 90: 26-31. PMID: 15546911, DOI: 10.1210/jc.2004-0179.Peer-Reviewed Original ResearchMeSH KeywordsAdultBone ResorptionCalciumDietary ProteinsFemaleHumansIntestinal AbsorptionKineticsOsteogenesisConceptsHigh-protein dietUrinary calciumBone turnoverCalcium absorptionDual-stable calcium isotopesAdditional urinary calciumIntestinal calcium absorptionHealthy womenStable calcium isotopesBone balanceNonsignificant trendSkeletal resorptionCalcium kineticsAcid loadBone originProtein-induced effectsLevels of proteinRandom orderDietary proteinDietHypercalciuriaWomenExperimental dietsSignificant reductionCalcium
2002
High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5
Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5. New England Journal Of Medicine 2002, 346: 1513-1521. PMID: 12015390, DOI: 10.1056/nejmoa013444.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersBone DensityCase-Control StudiesChromosomes, Human, Pair 11FemaleGenes, DominantGenotypeHumansIntercellular Signaling Peptides and ProteinsLDL-Receptor Related ProteinsLow Density Lipoprotein Receptor-Related Protein-5MaleMandibleMutation, MissenseOsteogenesisPalatePedigreePoint MutationProteinsProto-Oncogene ProteinsRadiographyReceptors, LDLSignal TransductionSyndromeWnt ProteinsZebrafish ProteinsConceptsLow-density lipoprotein receptor-related protein 5Higher bone densityProtein 5Bone densityDevelopmental proteinsLipoprotein receptor-related protein 5Fruit flyGenetic analysisDeep mandibleWnt activityTorus palatinusWnt pathwayFunction mutationsWntMajor public health problemNormal glycineBiochemical analysisMutationsTreatment of osteoporosisHigh bone massPublic health problemCodon 171Potential targetAutosomal dominant syndromeGenes