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 ResearchDietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice
Hasan S, Ghani N, Zhao X, Good J, Huang A, Wrona H, Liu J, Liu C. Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice. Protein & Cell 2024, pwae014. PMID: 38512816, DOI: 10.1093/procel/pwae014.Peer-Reviewed Original ResearchCytosolic phospholipase A2White adipose tissue inflammationAdipose tissue inflammationTissue inflammationState of chronic low-grade inflammationChronic low-grade inflammationHFD-induced weight gainLow-grade inflammationAttenuation of inflammationMolecular targetsPotential therapeutic optionDevelopment of metabolic disordersProtective effect of pyruvateAdipogenic differentiation in vitroDiet-induced obesityNonalcoholic fatty liver diseaseDifferentiation in vitroDrug affinity responsive target stabilityFatty liver diseasePhospholipase A2Meta-inflammationTherapeutic optionsDrug responseGlobal ablationMultifactorial etiologyNav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis
Fu W, Vasylyev D, Bi Y, Zhang M, Sun G, Khleborodova A, Huang G, Zhao L, Zhou R, Li Y, Liu S, Cai X, He W, Cui M, Zhao X, Hettinghouse A, Good J, Kim E, Strauss E, Leucht P, Schwarzkopf R, Guo E, Samuels J, Hu W, Attur M, Waxman S, Liu C. Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis. Nature 2024, 625: 557-565. PMID: 38172636, PMCID: PMC10794151, DOI: 10.1038/s41586-023-06888-7.Peer-Reviewed Original ResearchVoltage-gated sodium channelsOA progressionDorsal root ganglion neuronsStructural joint damagePain relief treatmentHuman OA chondrocytesCommon joint diseaseMultiple mouse modelsNav1.7 blockersPain behaviorGanglion neuronsPharmacological blockadeJoint damageJoint degenerationChannel blockersJoint diseaseOA chondrocytesMouse modelTherapeutic targetOsteoarthritisIntracellular Ca2Nav1.7Nav1.7 channelsGenetic ablationLimited evidence
2023
Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances
Huang G, Jian J, Liu C. Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances. Cytokine & Growth Factor Reviews 2023, 76: 142-159. PMID: 37981505, PMCID: PMC10978308, DOI: 10.1016/j.cytogfr.2023.11.001.Peer-Reviewed Original ResearchDiverse functionsRegulation of tumorigenesisChaperone activityMultiple membrane receptorsMultitude of processesGrowth factor-like moleculesExtracellular functionsNeuronal degenerative diseasesLysosomal proteinsIntricate mechanismsLysosomal functionMembrane receptorsIntracellular componentsLysosomal hydrolasesDiverse arrayLysosomal storage diseaseProteinNeural proliferationGRN geneCritical roleGrowth factorIntricate interplayRole of progranulinPathophysiological processesStorage diseaseInjectable hydrogel for sustained delivery of progranulin derivative Atsttrin in treating diabetic fracture healing
Moradi L, Witek L, Vivekanand Nayak V, Cabrera Pereira A, Kim E, Good J, Liu C. Injectable hydrogel for sustained delivery of progranulin derivative Atsttrin in treating diabetic fracture healing. Biomaterials 2023, 301: 122289. PMID: 37639975, PMCID: PMC11232488, DOI: 10.1016/j.biomaterials.2023.122289.Peer-Reviewed Original ResearchConceptsΒ-GP hydrogelPorous interconnected structureAmount of GOTissue engineering applicationsEngineering applicationsLong-term storage stabilityInjectable biomaterialsGrowth factor deliveryInjectable hydrogelsInterconnected structureHigh viscosityRapid sol-gel transitionHydrogelsSustained-release propertiesFactor deliveryBiomechanical environmentStorage stabilitySustained deliverySol-gel transitionExcellent candidateCartilage regenerationGel networkSustained releaseChitosanFracture healingUnraveling 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 osteoblastsOsteoporosisOsteoclastogenesisTau deficiency inhibits classically activated macrophage polarization and protects against collagen-induced arthritis in mice
Chen M, Fu W, Xu H, Liu C. Tau deficiency inhibits classically activated macrophage polarization and protects against collagen-induced arthritis in mice. Arthritis Research & Therapy 2023, 25: 146. PMID: 37559125, PMCID: PMC10410869, DOI: 10.1186/s13075-023-03133-4.Peer-Reviewed Original ResearchConceptsInflammatory cell infiltrationPro-inflammatory cytokinesRheumatoid arthritisAnkle jointSerum levelsCell infiltrationMacrophage polarizationOsteoclast activityCartilage damagePathogenesis of RACollagen-induced arthritis modelTau-/- miceCollagen-induced arthritisInflammatory joint diseasePro-inflammatory functionsProgression of CIAPotential therapeutic targetRole of tauInflammatory arthritisBone erosionArthritis incidenceBone lossClinical scoresArthritis modelInflammatory disorders
2022
PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases
Zhao X, Lin Y, Liou B, Fu W, Jian J, Fannin V, Zhang W, Setchell K, Grabowski G, Sun Y, Liu C. PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 120: e2210442120. PMID: 36574647, PMCID: PMC9910439, DOI: 10.1073/pnas.2210442120.Peer-Reviewed Original ResearchConceptsBlood-brain barrierParkinson's diseaseGaucher diseasePGRN deficiencyPD-like phenotypesRelevant mouse modelRare lysosomal storage diseaseCommon neurodegenerative disorderVisceral symptomsNeurobehavioral deficitsSevere neuroinflammationPD pathologyLysosomal storage diseaseTherapeutic studiesMouse modelNeuronopathic involvementProgranulinImpaired autophagyNeurodegenerative disordersGD phenotypeEarly onsetMiceDiseaseFirst linePathologyInjectable recombinant block polymer gel for sustained delivery of therapeutic protein in post traumatic osteoarthritis
Katyal P, Hettinghouse A, Meleties M, Hasan S, Chen C, Cui M, Sun G, Menon R, Lin B, Regatte R, Montclare J, Liu C. Injectable recombinant block polymer gel for sustained delivery of therapeutic protein in post traumatic osteoarthritis. Biomaterials 2022, 281: 121370. PMID: 35032910, PMCID: PMC9055922, DOI: 10.1016/j.biomaterials.2022.121370.Peer-Reviewed Original ResearchConceptsUnique stimuli-responsive propertiesProtein block polymersC gelStimuli-responsive propertiesProtein-based gelsSustained deliveryProtein-based biomaterialsBlock polymersPolymer gelsNetworked gelsProlonged releaseSynthetic materialsGelTherapeutic applicationsInjectable biomaterialsExcellent candidatePhysiological temperatureTherapeutic proteinsModular natureBiomaterialsBiomechanical environmentPolymersProspective therapeuticsRabbit anterior cruciate ligament transection (ACLT) modelPenfluridol targets acid sphingomyelinase to inhibit TNF signaling and is therapeutic against inflammatory autoimmune diseases
Chen Y, Liu R, Cui Y, Hettinghouse A, Fu W, Zhang L, Zhang C, Liu C. Penfluridol targets acid sphingomyelinase to inhibit TNF signaling and is therapeutic against inflammatory autoimmune diseases. Arthritis Research & Therapy 2022, 24: 27. PMID: 35045889, PMCID: PMC8767691, DOI: 10.1186/s13075-021-02713-6.Peer-Reviewed Original ResearchConceptsInflammatory autoimmune diseaseAnti-TNF activityNF-κB activationInflammatory arthritisAutoimmune diseasesAcid sphingomyelinase activityTherapeutic effectTumor necrosis factor αInhibitory effectTNFα-transgenic miceCollagen-induced arthritisSeverity of arthritisInflammatory cytokine productionM1 macrophage polarizationBone marrow-derived macrophagesNecrosis factor αNF-κB activitySphingomyelinase activitySmall molecule drug libraryRAW 264.7 macrophage cell lineMarrow-derived macrophagesAcid sphingomyelinaseDrug affinity responsive target stabilityCytokine productionChronic schizophrenia
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 ResearchIn Vitro Physical and Functional Interaction Assays to Examine the Binding of Progranulin Derivative Atsttrin to TNFR2 and Its Anti-TNFα Activity
Fu W, Hettinghouse A, Liu C. In Vitro Physical and Functional Interaction Assays to Examine the Binding of Progranulin Derivative Atsttrin to TNFR2 and Its Anti-TNFα Activity. Methods In Molecular Biology 2020, 2248: 109-119. PMID: 33185871, PMCID: PMC8112733, DOI: 10.1007/978-1-0716-1130-2_8.Peer-Reviewed Original ResearchConceptsAnti-TNFα activityAutoimmune diseasesTartrate-resistant acid phosphatase (TRAP) stainingAnti-TNFα therapyCollagen-induced arthritisInflammatory disease modelsGood therapeutic effectAcid phosphatase stainingGrowth factor-like moleculesTNF inhibitorsTherapeutic effectTNFα activityProgranulinFunctional inhibitionTNFR2AtsttrinDisease modelsPhosphatase stainingTNFRTNFαDiseaseInhibitionCritical roleDirect bindingHigh affinityMonitoring 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