2024
Mitofusin 2 plays a critical role in maintaining the functional integrity of the neuromuscular-skeletal axis
Zhu M, Zeiss C, Hamrick M, Weinstein R, Sun B, Brotto M, Liu X, Siu E, Huttner A, Tommasini S, Simpson C, Insogna K. Mitofusin 2 plays a critical role in maintaining the functional integrity of the neuromuscular-skeletal axis. Bone 2024, 184: 117086. PMID: 38552893, DOI: 10.1016/j.bone.2024.117086.Peer-Reviewed Original ResearchConceptsDeletion of Mfn2Bone mineral densityMitofusin 2Reduced expression of Mfn2Myofiber atrophySpinal cordTransgenic mice expressing CreMice expressing CreNon-redundant roleSkeletal muscle histologyLumbar spinal cordTrabecular bone massLean body massExpression of Mfn2Mitochondrial reticulumMFN2 geneDisruption of cellular architectureImpaired osteoblast differentiationOsteoblast lineage commitmentMfn2Mitochondrial sizeMitofusinMineral densityCo-expressionDisorganized sarcomeres
2023
Bone marrow sinusoidal endothelial cells are a site of Fgf23 upregulation in a mouse model of iron deficiency anemia
Li X, Lozovatsky L, Tommasini S, Fretz J, Finberg K. Bone marrow sinusoidal endothelial cells are a site of Fgf23 upregulation in a mouse model of iron deficiency anemia. Blood Advances 2023, 7: 5156-5171. PMID: 37417950, PMCID: PMC10480544, DOI: 10.1182/bloodadvances.2022009524.Peer-Reviewed Original ResearchConceptsSinusoidal endothelial cellsEndothelial cellsBone marrowBM sectionsFGF23 upregulationFibroblast growth factor 23Iron deficiencyElevated serum erythropoietinFGF23 promoter activityBM endothelial cellsGrowth factor 23Vitamin D metabolismIron deficiency anemiaSystemic iron deficiencyKnockout mice exhibitBone marrow sinusoidal endothelial cellsNormal iron balanceNonanemic controlsChronic anemiaFactor 23D metabolismEndothelial cell populationErythropoietin treatmentDeficiency anemiaMouse modelSingle‐Cell Transcriptomics of Bone Marrow Stromal Cells in Diversity Outbred Mice: A Model for Population‐Level scRNA‐Seq Studies
Dillard L, Rosenow W, Calabrese G, Mesner L, Al‐Barghouthi B, Abood A, Farber E, Onengut‐Gumuscu S, Tommasini S, Horowitz M, Rosen C, Yao L, Qin L, Farber C. Single‐Cell Transcriptomics of Bone Marrow Stromal Cells in Diversity Outbred Mice: A Model for Population‐Level scRNA‐Seq Studies. Journal Of Bone And Mineral Research 2023, 38: 1350-1363. PMID: 37436066, PMCID: PMC10528806, DOI: 10.1002/jbmr.4882.Peer-Reviewed Original ResearchConceptsGene regulatory networksMesenchymal lineage cellsBone marrow-derived stromal cellsGenome-wide association studiesOsteocyte-like cellsLineage cellsOsteogenic conditionsTranscriptomic profilesSingle-cell RNA-seqCell typesTranscriptomic data setsGenetics of osteoporosisDisease-associated variantsSingle-cell levelMarrow-derived stromal cellsTranscriptomic perspectiveRegulatory networksCausal genesRNA-seqTranscriptomic dataScRNA-seqMesenchymal progenitorsAssociation studiesGenetic studiesLineage precursors
2019
High dose vitamin D supplementation does not rescue bone loss following Roux-en-Y gastric bypass in female rats
Niu A, Carpenter TO, Grams JM, Bozorgmehri S, Tommasini SM, Schafer AL, Canales BK. High dose vitamin D supplementation does not rescue bone loss following Roux-en-Y gastric bypass in female rats. Bone 2019, 127: 172-180. PMID: 31226531, PMCID: PMC6708762, DOI: 10.1016/j.bone.2019.06.015.Peer-Reviewed Original ResearchConceptsCalcium/creatinine ratioVitamin D supplementationSecondary hyperparathyroidismBone lossD supplementationGastric bypassGut hormonesRYGB groupParathyroid hormoneFracture riskFemale ratsUrine calcium/creatinine ratioBone volumeUrinary calcium/creatinine ratioHigh-dose vitamin D supplementationAdequate vitamin D supplementationC-terminal telopeptide (CTX) levelsHigher serum parathyroid hormoneIU vitamin D supplementationIU vitamin D/Bone phenotypeDose vitamin D supplementationResultant secondary hyperparathyroidismVitamin D/Serum parathyroid hormone
2017
Ibuprofen impairs capsulolabral healing in a rat model of anterior glenohumeral instability
Packer JD, Varthi AG, Zhu DS, Javier FG, Young JD, Garver JV, Henry H, Tommasini SM, Blaine TA. Ibuprofen impairs capsulolabral healing in a rat model of anterior glenohumeral instability. Journal Of Shoulder And Elbow Surgery 2017, 27: 315-324. PMID: 29195899, DOI: 10.1016/j.jse.2017.09.027.Peer-Reviewed Original ResearchConceptsNonsteroidal anti-inflammatory drugsNSAID groupGlenohumeral dislocationRat modelControl groupUninjured limbUse of NSAIDsGlenohumeral instabilityGlenoid labrumAnterior glenohumeral dislocationAnterior-inferior labral tearsAnterior glenohumeral instabilityAnti-inflammatory drugsMatched pair analysisNew rat modelPersistent shoulder instabilityCapsular healingPostinjury administrationInjured limbImpaired healingLabral tearsHistologic analysisShoulder instabilityGlenohumeral stabilityBiomechanical testing
2016
Integrating GWAS and Co-expression Network Data Identifies Bone Mineral Density Genes SPTBN1 and MARK3 and an Osteoblast Functional Module
Calabrese GM, Mesner LD, Stains JP, Tommasini SM, Horowitz MC, Rosen CJ, Farber CR. Integrating GWAS and Co-expression Network Data Identifies Bone Mineral Density Genes SPTBN1 and MARK3 and an Osteoblast Functional Module. Cell Systems 2016, 4: 46-59.e4. PMID: 27866947, PMCID: PMC5269473, DOI: 10.1016/j.cels.2016.10.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone and BonesBone DensityChromosome MappingGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMiceMice, Inbred C57BLMice, KnockoutOsteoblastsOsteoporosisOsteoporotic FracturesPhenotypePolymorphism, Single NucleotideProtein Serine-Threonine KinasesSpectrinTranscriptomeConceptsGenome-wide association studiesCo-expression networkGWAS lociCausal genesBMD genome-wide association studiesIntegrating Genome-Wide Association StudyBMD GWAS lociGWAS associationsMapping genesGWAS dataAssociation studiesGenesLociFunctional modulesHeritable predictorSPTBN1Most associationsWide rangeNovel anatomic adaptation of cortical bone to meet increased mineral demands of reproduction
Macica CM, King HE, Wang M, McEachon CL, Skinner CW, Tommasini SM. Novel anatomic adaptation of cortical bone to meet increased mineral demands of reproduction. Bone 2016, 85: 59-69. PMID: 26825813, PMCID: PMC7429445, DOI: 10.1016/j.bone.2015.12.056.Peer-Reviewed Original ResearchConceptsHyp miceMineral homeostasisElevated serum PTHMaternal bone massMineralized trabecular boneIntestinal calcium absorptionCortical boneWild-type miceSerum PTHCalcitriol productionFemale patientsMaternal skeletonPostnatal nutritionCalcium absorptionBone resorptionFracture riskMaternal adaptationBone massBone fragilityMurine modelIntracortical porosityUnaffected miceMouse modelMMP-13Fetal development
2015
Deletion of Rac in Mature Osteoclasts Causes Osteopetrosis, an Age‐Dependent Change in Osteoclast Number, and a Reduced Number of Osteoblasts In Vivo
Zhu M, Sun B, Saar K, Simpson C, Troiano N, Dallas SL, Tiede‐Lewis L, Nevius E, Pereira JP, Weinstein RS, Tommasini SM, Insogna KL. Deletion of Rac in Mature Osteoclasts Causes Osteopetrosis, an Age‐Dependent Change in Osteoclast Number, and a Reduced Number of Osteoblasts In Vivo. Journal Of Bone And Mineral Research 2015, 31: 864-873. PMID: 26496249, PMCID: PMC4826801, DOI: 10.1002/jbmr.2733.Peer-Reviewed Original ResearchConceptsDual-energy X-ray absorptiometryBone mineral densityDKO miceParathyroid hormoneOsteoclast numberDKO animalsSerum cross-linked C-telopeptideCross-linked C-telopeptideDaily parathyroid hormoneTrabecular bone massX-ray absorptiometryMetaphyseal trabecular boneNormal differentiation markersAge-dependent changesC-telopeptideMineral densityBone massBone densityActin ring formationSkeletal metabolismOsteoblast numberTooth eruptionResorptive activityNormal responseFocal disruptionPeriosteal PTHrP Regulates Cortical Bone Remodeling During Fracture Healing
Wang M, Nasiri AR, Broadus AE, Tommasini SM. Periosteal PTHrP Regulates Cortical Bone Remodeling During Fracture Healing. Bone 2015, 81: 104-111. PMID: 26164475, PMCID: PMC4641003, DOI: 10.1016/j.bone.2015.07.008.Peer-Reviewed Original ResearchConceptsFracture healingPTHrP expressionCKO miceCortical bone surfaceFracture repairTibial fracture surgeryRole of PTHrPHormone-related proteinTibial fracture modelCartilaginous callus formationConditional knockout miceBone surfaceCortical bone remodelingType I receptorCD1 controlsFracture surgeryCD1 miceKnockout miceInitial genetic evidencePTHrPOsteoblastic activityBone remodelingMiceBone mineralizationI receptor
2014
Periosteal PTHrP regulates cortical bone modeling during linear growth in mice
Wang M, VanHouten JN, Nasiri AR, Tommasini SM, Broadus AE. Periosteal PTHrP regulates cortical bone modeling during linear growth in mice. Journal Of Anatomy 2014, 225: 71-82. PMID: 24762197, PMCID: PMC4073294, DOI: 10.1111/joa.12184.Peer-Reviewed Original ResearchConceptsMetaphyseal-diaphyseal junctionParathyroid hormone-related peptideEndocortical bone formationCD-1 miceNF-kB ligandHormone-related peptideMineral apposition rateCortical bone modelingEntire boneLinear growthAnteromedial cortexCKO miceProximal tibiaLateral tibiaReceptor activatorOC numberApposition rateOsteoclastic resorptionPTHrPBone modelingBone formationFibulaLong bonesMicePeriosteumThe Transcription Factor T-box 3 Regulates Colony-stimulating Factor 1-dependent Jun Dimerization Protein 2 Expression and Plays an Important Role in Osteoclastogenesis*
Yao C, Yao GQ, Sun BH, Zhang C, Tommasini SM, Insogna K. The Transcription Factor T-box 3 Regulates Colony-stimulating Factor 1-dependent Jun Dimerization Protein 2 Expression and Plays an Important Role in Osteoclastogenesis*. Journal Of Biological Chemistry 2014, 289: 6775-6790. PMID: 24394418, PMCID: PMC3945339, DOI: 10.1074/jbc.m113.499210.Peer-Reviewed Original Research
2013
The remarkable migration of the medial collateral ligament
Wang M, Nasiri A, VanHouten JN, Tommasini SM, Broadus AE. The remarkable migration of the medial collateral ligament. Journal Of Anatomy 2013, 224: 490-498. PMID: 24266550, PMCID: PMC3954274, DOI: 10.1111/joa.12145.Peer-Reviewed Original ResearchConceptsMedial collateral ligamentMigratory tractsCollateral ligamentParathyroid hormone-related proteinOsteoclastic bone resorptionHormone-related proteinCortical surfaceInsertions of tendonsInsertion siteBone resorptionLong bone growthPTHrP functionsOsteoclastic activityPeriosteal osteoclastsRegulatory moleculesOsteoblast activityGrowth spurtLong bonesOsteoclastsCortical boneLigamentRecent evidenceHistological techniquesBone surfaceTract
2012
Genetic variations and physical activity as determinants of limb bone morphology: An experimental approach using a mouse model
Wallace IJ, Tommasini SM, Judex S, Garland T, Demes B. Genetic variations and physical activity as determinants of limb bone morphology: An experimental approach using a mouse model. American Journal Of Biological Anthropology 2012, 148: 24-35. PMID: 22331623, DOI: 10.1002/ajpa.22028.Peer-Reviewed Original Research
2011
Changes in intracortical microporosities induced by pharmaceutical treatment of osteoporosis as detected by high resolution micro-CT
Tommasini SM, Trinward A, Acerbo AS, De Carlo F, Miller LM, Judex S. Changes in intracortical microporosities induced by pharmaceutical treatment of osteoporosis as detected by high resolution micro-CT. Bone 2011, 50: 596-604. PMID: 22226688, PMCID: PMC3278519, DOI: 10.1016/j.bone.2011.12.012.Peer-Reviewed Original ResearchConceptsAge-matched controlsUntreated OVXEstrogen withdrawalSix-month-old female SpragueDifferent osteoporosis treatmentsUntreated OVX ratsStart of treatmentEndosteal regionOsteocyte lacunar sizeEffect of treatmentOVX ratsOsteoporosis treatmentFemale SpraguePTH treatmentDawley ratsCurrent treatmentNumber of lacunaeMedial cortexOsteocyte lacunaePharmaceutical treatmentOVXMedial quadrantAlendronateBone strengthFemoral diaphysis
2009
Phenotypic Integration Among Trabecular and Cortical Bone Traits Establishes Mechanical Functionality of Inbred Mouse Vertebrae*
Tommasini SM, Hu B, Nadeau JH, Jepsen KJ. Phenotypic Integration Among Trabecular and Cortical Bone Traits Establishes Mechanical Functionality of Inbred Mouse Vertebrae*. Journal Of Bone And Mineral Research 2009, 24: 606-620. PMID: 19063678, PMCID: PMC2659510, DOI: 10.1359/jbmr.081224.Peer-Reviewed Original ResearchConceptsQuantitative trait lociBody sizeBone traitsPhenotypic integrationTrait covariationComplex traitsTrait lociMultiple traitsGenetic analysisDifferent traitsEnvironmental perturbationsSkeletal traitsTrabecular traitsAXB/BXAC57BL/6J genomeRI panelNonrandom setTraitsCompensatory interactionsGenetic variantsAdaptive responseB6 genomeRelative amountsGenomeCompositional traits
2008
Phenotypic integration of skeletal traits during growth buffers genetic variants affecting the slenderness of femora in inbred mouse strains
Jepsen KJ, Hu B, Tommasini SM, Courtland HW, Price C, Cordova M, Nadeau JH. Phenotypic integration of skeletal traits during growth buffers genetic variants affecting the slenderness of femora in inbred mouse strains. Mammalian Genome 2008, 20: 21. PMID: 19082857, PMCID: PMC2650248, DOI: 10.1007/s00335-008-9158-1.Peer-Reviewed Original ResearchConceptsGenetic variantsSkeletal traitsFunctional interactionMatrix mineralizationCompensatory interactionsGenotype-phenotype relationshipsPhenotypic integrationAdult traitsLoss of functionBiological controlPrecise regulationMouse strainsAXB/BXASusceptibility genesInner bone surfaceTraitsEnvironmental variantsPostnatal growthNew insightsBone slendernessQuantitative expectationsVariantsGrowthSkeletal growthExpansion rate
2007
Percolation theory relates corticocancellous architecture to mechanical function in vertebrae of inbred mouse strains
Tommasini SM, Wearne SL, Hof PR, Jepsen KJ. Percolation theory relates corticocancellous architecture to mechanical function in vertebrae of inbred mouse strains. Bone 2007, 42: 743-750. PMID: 18258502, PMCID: PMC2650241, DOI: 10.1016/j.bone.2007.12.009.Peer-Reviewed Original ResearchGenetic randomization reveals functional relationships among morphologic and tissue-quality traits that contribute to bone strength and fragility
Jepsen KJ, Hu B, Tommasini SM, Courtland HW, Price C, Terranova CJ, Nadeau JH. Genetic randomization reveals functional relationships among morphologic and tissue-quality traits that contribute to bone strength and fragility. Mammalian Genome 2007, 18: 492-507. PMID: 17557179, PMCID: PMC1998883, DOI: 10.1007/s00335-007-9017-5.Peer-Reviewed Original ResearchConceptsFunctional interactionMean trait valuesRI strainsCombination of traitsTrait valuesGenomic regionsCellular processesLoss of functionBone slendernessGenetic variabilityEnvironmental perturbationsSkeletal traitsAXB/BXAImportant functional interactionTraitsBiological paradigmBone traitsFunctional relationshipMouse strainsGenetic randomizationAdult malesHigher mineral densityStrainsUnique setGrowth
2005
Genetic Variation in Structure‐Function Relationships for the Inbred Mouse Lumbar Vertebral Body*
Tommasini SM, Morgan TG, van der Meulen MCh, Jepsen KJ. Genetic Variation in Structure‐Function Relationships for the Inbred Mouse Lumbar Vertebral Body*. Journal Of Bone And Mineral Research 2005, 20: 817-827. PMID: 15824855, DOI: 10.1359/jbmr.041234.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsBiomechanical PhenomenaBone and BonesFemaleGenetic VariationLumbar VertebraeMiceMice, Inbred C3HMice, Inbred C57BLMice, Inbred StrainsModels, AnatomicModels, BiologicalModels, GeneticMultivariate AnalysisPhenotypeSpecies SpecificityStress, MechanicalStructure-Activity RelationshipTensile StrengthTomography, X-Ray ComputedConceptsMechanical propertiesBone mechanical propertiesTrabecular bone tissueWhole bone mechanical propertiesMeasure of ductilityTotal deformationFailure loadVertebral mechanical propertiesBone tissueIsotropic voxel sizeBiomechanical analysisImaging systemPropertiesDuctilityStructure-function relationshipsVoxel sizeDeformationBV/TVStiffness