2024
Novel peptide inhibitor of human tumor necrosis factor-α has antiarthritic activity
Sahu D, Gupta C, Yennamalli R, Sharma S, Roy S, Hasan S, Gupta P, Sharma V, Kashyap S, Kumar S, Dwivedi V, Zhao X, Panda A, Das H, Liu C. Novel peptide inhibitor of human tumor necrosis factor-α has antiarthritic activity. Scientific Reports 2024, 14: 12935. PMID: 38839973, PMCID: PMC11153517, DOI: 10.1038/s41598-024-63790-6.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsGel mobility-shift assaysCollagen-induced arthritisMobility-shift assaysCell surface receptorsFluorescence-activated cell sortingSequence strandsBinding of TNFIn silico methodsCell deathMouse modelSurface receptorsNuclear translocationTrimer formationCell culture assaysRheumatoid arthritisVicious cycle of inflammationModel of collagen-induced arthritisTumor necrosis factor-aCell sortingMouse model of collagen-induced arthritisA549 cellsCycle of inflammationInflammatory bone destructionCulture assayHow do small quantities of cartilage sodium channels play a significant role in osteoarthritis?
Kong X, Liu C. How do small quantities of cartilage sodium channels play a significant role in osteoarthritis? Clinical And Translational Medicine 2024, 14: e1634. PMID: 38530147, PMCID: PMC10964914, DOI: 10.1002/ctm2.1634.Peer-Reviewed Original ResearchHumansOsteoarthritis
2023
Unraveling the mechanisms behind joint damage
Fu W, Liu C. Unraveling the mechanisms behind joint damage. ELife 2023, 12: e89778. PMID: 37366155, PMCID: PMC10299819, DOI: 10.7554/elife.89778.Peer-Reviewed Original ResearchPathogenic mechanisms of glucocorticoid-induced osteoporosis
Chen M, Fu W, Xu H, Liu C. Pathogenic mechanisms of glucocorticoid-induced osteoporosis. Cytokine & Growth Factor Reviews 2023, 70: 54-66. PMID: 36906448, PMCID: PMC10518688, DOI: 10.1016/j.cytogfr.2023.03.002.Peer-Reviewed Original ResearchConceptsGlucocorticoid-induced osteoporosisExogenous glucocorticoidsGC excessBone cellsBone formationImpaired bone formationMultiple adverse effectsLong-term useExcessive glucocorticoidsAutoimmune diseasesBone resorptionPrescribed medicinesEnhanced osteoclastogenesisPathogenic mechanismsProcess of osteoblastogenesisGlucocorticoidsHigh dosesOsteoclast apoptosisApoptosis of osteoblastsMature osteoclastsAdverse effectsOsteoclastsDifferentiation of osteoblastsOsteoporosisOsteoclastogenesis
2021
Digoxin targets low density lipoprotein receptor-related protein 4 and protects against osteoarthritis
Wang K, Ding X, Jiang N, Zeng C, Wu J, Cai X, Hettinghouse A, Khleborodova A, Lei Z, Chen Z, Lei G, Liu C. Digoxin targets low density lipoprotein receptor-related protein 4 and protects against osteoarthritis. Annals Of The Rheumatic Diseases 2021, 81: 544-555. PMID: 34853001, PMCID: PMC9082564, DOI: 10.1136/annrheumdis-2021-221380.Peer-Reviewed Original ResearchConceptsLow-density lipoprotein receptor-related protein 4Lipoprotein receptor-related protein 4Digoxin useCohort studyChondroprotective actionChondrocyte anabolismHealth Improvement NetworkProtein 4Risk of osteoarthritisPathogenesis of osteoarthritisBinding of digoxinAtrial fibrillationChondroprotective effectsJoint osteoarthritisTherapeutic effectSerial screeningOA modelImprovement NetworkOsteoarthritisDrug AdministrationChondrocyte catabolismDigoxinJoint replacementNovel targetPotential stimulatorProgranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease
Zhao X, Liberti R, Jian J, Fu W, Hettinghouse A, Sun Y, Liu C. Progranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease. Journal Of Molecular Medicine 2021, 99: 1639-1654. PMID: 34453183, PMCID: PMC8541919, DOI: 10.1007/s00109-021-02127-6.Peer-Reviewed Original ResearchConceptsLysosomal storage diseaseGaucher diseaseAutophagosome-lysosome fusionCommon lysosomal storage diseasePGRN deficiencyNovel therapiesAnimal modelsProgranulinLC3-IIMolecular targetsCrucial mediatorCritical moleculesStorage diseaseDiseaseAutophagic fluxC-terminal fragmentImpaired fusionPatient fibroblastsAutophagyImpairmentKey regulatorTNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity
Fu W, Hu W, Yi Y, Hettinghouse A, Sun G, Bi Y, He W, Zhang L, Gao G, Liu J, Toyo-oka K, Xiao G, Solit D, Loke P, Liu C. TNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity. Journal Of Clinical Investigation 2021, 131 PMID: 34185706, PMCID: PMC8363273, DOI: 10.1172/jci144016.Peer-Reviewed Original ResearchConceptsMacrophage polarizationMacrophage plasticityPI3K/Akt/mTORPathogenesis of inflammationMyeloid-specific deletionNF-κB activationAkt/mTORInflammatory arthritisAntiinflammatory pathwayImmunoregulatory roleAutoimmune diseasesProtective effectTherapeutic implicationsInflammationTNFR2 signalingAutoimmunityTNFR2TNFR2 activationReceptor complexDiseaseIntracellular regulatorsActivationMolecule 14TNFR1Arthritis14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis
Fu W, Hettinghouse A, Chen Y, Hu W, Ding X, Chen M, Ding Y, Mundra J, Song W, Liu R, Yi Y, Attur M, Samuels J, Strauss E, Leucht P, Schwarzkopf R, Liu C. 14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis. Annals Of The Rheumatic Diseases 2021, 80: 1615-1627. PMID: 34226187, PMCID: PMC8595573, DOI: 10.1136/annrheumdis-2021-220000.Peer-Reviewed Original ResearchConceptsPathogenesis of osteoarthritisTNFR2 complexTherapeutic effectSingle-cell RNA-seqIntracellular componentsReceptor complexExtracellular signal-regulated kinaseNuclear factor kappa BSignal-regulated kinaseCommon joint diseaseFactor kappa BChondrocyte-specific deletionProteomic screenElk-1RNA-seqTranscription factorsCell-based assaysTNF signalingTNFR2 pathwayInducible componentJoint diseaseActivity screenTherapeutic targetKappa BOsteoarthritisProgranulin promotes bone fracture healing via TNFR pathways in mice with type 2 diabetes mellitus
Ding Y, Wei J, Hettinghouse A, Li G, Li X, Einhorn T, Liu C. Progranulin promotes bone fracture healing via TNFR pathways in mice with type 2 diabetes mellitus. Annals Of The New York Academy Of Sciences 2021, 1490: 77-89. PMID: 33543485, PMCID: PMC8138780, DOI: 10.1111/nyas.14568.Peer-Reviewed Original ResearchConceptsType 2 diabetes mellitusRole of progranulinBone fracture healingFracture healingDiabetes mellitusT2DM modelType 1 diabetic conditionAnti-inflammatory activityTranscription-polymerase chain reactionLocal administrationBone marrow cellsExogenous progranulinMKR micePGRN effectsPrimary bone marrow cellsFracture riskDiabetic conditionsPGRN mRNABone fragilityImmunohistochemical stainingMetabolic disordersRecombinant progranulinBone fracturesProgranulinTherapeutic potential
2020
Repurposing FDA-approved drugs for SARS-CoV-2 through an ELISA-based screening for the inhibition of RBD/ACE2 interaction
Fu W, Chen Y, Wang K, Hettinghouse A, Hu W, Wang J, Lei Z, Chen Z, Stapleford K, Liu C. Repurposing FDA-approved drugs for SARS-CoV-2 through an ELISA-based screening for the inhibition of RBD/ACE2 interaction. Protein & Cell 2020, 12: 586-591. PMID: 33210243, PMCID: PMC7673315, DOI: 10.1007/s13238-020-00803-w.Peer-Reviewed Original ResearchMonitoring Atsttrin-Mediated Inhibition of TNFα/NF-κβ Activation Through In Vivo Bioluminescence Imaging
Hettinghouse A, Fu W, Liu C. Monitoring Atsttrin-Mediated Inhibition of TNFα/NF-κβ Activation Through In Vivo Bioluminescence Imaging. Methods In Molecular Biology 2020, 2248: 201-210. PMID: 33185877, PMCID: PMC8140391, DOI: 10.1007/978-1-0716-1130-2_14.Peer-Reviewed Original ResearchConceptsTumor necrosis factorDouble mutant miceNF-κBOverexpression of TNFMutant miceBioluminescence imagingTransgenic reporter mouse modelNF-κB luciferaseNF-κβ activationVivo bioluminescence imagingReporter mouse modelAutoimmune conditionsTNF-TgNF-κβNecrosis factorImmune responseMouse modelMolecular mediatorsTransgenic modelTherapeutic objectivesVivo efficacyProgranulinPotential therapeuticsAtsttrinLuciferase activity
2019
Progranulin promotes diabetic fracture healing in mice with type 1 diabetes
Wei J, Zhang L, Ding Y, Liu R, Guo Y, Hettinghouse A, Buza J, De La Croix J, Li X, Einhorn T, Liu C. Progranulin promotes diabetic fracture healing in mice with type 1 diabetes. Annals Of The New York Academy Of Sciences 2019, 1460: 43-56. PMID: 31423598, PMCID: PMC8138779, DOI: 10.1111/nyas.14208.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChondrogenesisDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Extracellular Signal-Regulated MAP KinasesFracture HealingGene DeletionHumansInflammationMiceProgranulinsProto-Oncogene Proteins c-aktReceptors, Tumor Necrosis FactorRecombinant ProteinsSignal TransductionTOR Serine-Threonine KinasesTumor Necrosis Factor-alphaConceptsDiabetic fracture healingFracture healingTumor necrosis factor receptorProinflammatory cytokine tumor necrosisType 1 diabetes mellitusAnti-inflammatory signaling pathwaysCytokine tumor necrosisType 1 diabetesNovel therapeutic intervention strategiesGrowth factor-like moleculesTherapeutic intervention strategiesNecrosis factor receptorDiabetic fractureBone fracture healingDiabetes mellitusInsulin deficiencyAutoimmune diseasesTumor necrosisTherapeutic effectBone fracturesVivo modelDiabetesFactor receptorHealingIntervention strategiesProgranulin: A conductor of receptors orchestra, a chaperone of lysosomal enzymes and a therapeutic target for multiple diseases
Cui Y, Hettinghouse A, Liu C. Progranulin: A conductor of receptors orchestra, a chaperone of lysosomal enzymes and a therapeutic target for multiple diseases. Cytokine & Growth Factor Reviews 2019, 45: 53-64. PMID: 30733059, PMCID: PMC6450552, DOI: 10.1016/j.cytogfr.2019.01.002.Peer-Reviewed Original ResearchConceptsTherapeutic targetInflammatory autoimmune diseaseRare lysosomal storage diseaseCommon neurological diseasesPromising therapeutic targetPreclinical disease modelsDrug development strategiesExtracellular progranulinAutoimmune diseasesClinical trialsLysosomal storage diseaseTherapeutic strategiesNeurological diseasesKinds of diseasesProgranulinDiseaseDisease modelsStorage diseaseMultiple membrane receptorsPathological statesTissue repairMultiple diseasesLysosomal enzymesPleiotropic functionsDiverse pathological statesClinical Application of Teriparatide in Fracture Prevention: A Systematic Review.
Chen Y, Liu R, Hettinghouse A, Wang S, Liu G, Liu C. Clinical Application of Teriparatide in Fracture Prevention: A Systematic Review. JBJS Reviews 2019, 7: e10. PMID: 30694878, DOI: 10.2106/jbjs.rvw.18.00052.Peer-Reviewed Original ResearchConceptsNonvertebral fracturesParathyroid hormoneFracture preventionOsteoporotic patientsSystematic reviewSelective estrogen receptor modulatorsChronic kidney diseaseSystematic Reviews 2Estrogen receptor modulatorsPostmenopausal statusAdverse eventsRANKL inhibitorGlucocorticoid treatmentOvid EmbaseCochrane LibraryKidney diseaseFracture riskEligible studiesStrontium ranelateOvid MEDLINEReceptor modulatorsTeriparatideOsteoporotic individualsHigh riskAnabolic agents
2018
Brain-penetrant heat shock protein amplifier arimoclomol enhances GCase activity in in vitro Gaucher disease models
Hettinghouse A, Liu C. Brain-penetrant heat shock protein amplifier arimoclomol enhances GCase activity in in vitro Gaucher disease models. EBioMedicine 2018, 38: 7-8. PMID: 30522930, PMCID: PMC6306393, DOI: 10.1016/j.ebiom.2018.11.052.Peer-Reviewed Original ResearchProgranulin associates with hexosaminidase A and ameliorates GM2 ganglioside accumulation and lysosomal storage in Tay-Sachs disease
Chen Y, Jian J, Hettinghouse A, Zhao X, Setchell K, Sun Y, Liu C. Progranulin associates with hexosaminidase A and ameliorates GM2 ganglioside accumulation and lysosomal storage in Tay-Sachs disease. Journal Of Molecular Medicine 2018, 96: 1359-1373. PMID: 30341570, PMCID: PMC6240367, DOI: 10.1007/s00109-018-1703-0.Peer-Reviewed Original ResearchTargeting tumor necrosis factor receptors in ankylosing spondylitis
Lata M, Hettinghouse A, Liu C. Targeting tumor necrosis factor receptors in ankylosing spondylitis. Annals Of The New York Academy Of Sciences 2018, 1442: 5-16. PMID: 30008173, PMCID: PMC6333510, DOI: 10.1111/nyas.13933.Peer-Reviewed Original ResearchConceptsRole of TNFTumor necrosis factor inhibitorsCourse of ASTargeted biologic therapiesAnti-TNF therapyAutoimmune inflammatory disorderNecrosis factor inhibitorsMore effective treatment strategiesSerious adverse effectsMultiple clinical trialsEffective treatment strategiesPathogenesis of ASTumor necrosis factor receptorNecrosis factor receptorBiologic therapyTNF inhibitorsFactor inhibitorsInflammatory disordersPathogenic roleClinical trialsTreatment strategiesImmune pathwaysTNFTNF biologyTherapyMolecular regulations and therapeutic targets of Gaucher disease
Chen Y, Sud N, Hettinghouse A, Liu C. Molecular regulations and therapeutic targets of Gaucher disease. Cytokine & Growth Factor Reviews 2018, 41: 65-74. PMID: 29699937, PMCID: PMC8108120, DOI: 10.1016/j.cytogfr.2018.04.003.Peer-Reviewed Original ResearchConceptsGaucher diseaseHeat shock proteinsProper foldingMolecular regulationActivity of GCaseLysosomal localizationShock proteinsCommon lysosomal storage diseaseLysosomal appearanceIon channelsCalcium ion channelsLysosomal accumulationSaposin CLysosomal storage diseaseSubstrate glucosylceramideInflammatory mediatorsProinflammatory moleculesNew targetsPathogenic mechanismsTherapeutic targetGCaseNovel moleculesSmall moleculesDiseaseStorage diseaseChitinase-3-like Protein 1: A Progranulin Downstream Molecule and Potential Biomarker for Gaucher Disease
Jian J, Chen Y, Liberti R, Fu W, Hu W, Saunders-Pullman R, Pastores G, Chen Y, Sun Y, Grabowski G, Liu C. Chitinase-3-like Protein 1: A Progranulin Downstream Molecule and Potential Biomarker for Gaucher Disease. EBioMedicine 2018, 28: 251-260. PMID: 29396296, PMCID: PMC5835567, DOI: 10.1016/j.ebiom.2018.01.022.Peer-Reviewed Original ResearchConceptsGD patientsHealthy controlsGaucher diseaseDownstream moleculesExpression of CHI3L1Serum CHI3L1Serum levelsPGRN levelsTherapeutic effectClinical biomarkersPatientsPotential biomarkersNull miceCHI3L1ProgranulinElevated levelsBiomarkersWhole-genome microarraysDiseaseCHIT1Genome microarraysNovel regulatorImmunohistochemistryLevelsMice
2017
Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models
Wei J, Fu W, Ding Y, Hettinghouse A, Lendhey M, Schwarzkopf R, Kennedy O, Liu C. Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models. Arthritis Research & Therapy 2017, 19: 280. PMID: 29258611, PMCID: PMC5735869, DOI: 10.1186/s13075-017-1485-8.Peer-Reviewed Original ResearchConceptsTherapeutic effectOA modelPain-related markersAnti-catabolic effectsRole of progranulinDegenerative joint diseaseMurine OA modelMultiple murine modelsNew therapeutic alternativesTumor necrosis factor receptorIntra-articular deliveryNecrosis factor receptorInflammatory arthritisPGRN deficiencyOA phenotypeSafranin O stainingTherapeutic alternativeRat modelJoint diseaseOsteoarthritis progressionPreventative effectMurine modelCartilage degradationDegenerative factorsEarly osteoarthritis