Wenyu Fu
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Nav1.7 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 evidenceTNFR2/14-3-3ε 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 BOsteoarthritis
2024
Progranulin deficiency associates with postmenopausal osteoporosis via increasing ubiquitination of estrogen receptor α
Li G, Wang A, Tang W, Fu W, Tian Q, Jian J, Lata M, Hettinghouse A, Ding Y, Wei J, Zhao X, Wang M, Dong Q, Liu C, Xu Y. Progranulin deficiency associates with postmenopausal osteoporosis via increasing ubiquitination of estrogen receptor α. Genes & Diseases 2024, 101221. DOI: 10.1016/j.gendis.2024.101221.Peer-Reviewed Original ResearchPostmenopausal osteoporosisEstrogen receptorReceptor AEstrogen signalingTreatment of postmenopausal osteoporosisOvariectomy-induced bone lossEstrogen-mediated inhibitionRegulation of bone mineral densityBone mineral densityEstrogen receptor aPGRN-deficient miceInhibition of osteoclastogenesisPostmenopausal womenEstrogen deficiencyMineral densityLoss of progranulinEstrogen regulationBone lossBone massPositive feedback regulatory loopBone resorptionOsteoporosisTherapeutic approachesEstrogenOsteoporosis model
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 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 linePathologyPenfluridol 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
Roles and Mechanisms of Irisin in Attenuating Pathological Features of Osteoarthritis
Li X, Zhu X, Wu H, Van Dyke T, Xu X, Morgan E, Fu W, Liu C, Tu Q, Huang D, Chen J. Roles and Mechanisms of Irisin in Attenuating Pathological Features of Osteoarthritis. Frontiers In Cell And Developmental Biology 2021, 9: 703670. PMID: 34650969, PMCID: PMC8509718, DOI: 10.3389/fcell.2021.703670.Peer-Reviewed Original ResearchMechanisms of irisinOA progressionKI miceKO miceOA mouse modelIntra-articular injectionNovel therapeutic targetPrimary chondrocytesPathological tissue samplesInflammatory factorsOA pathogenesisPathological featuresIntraarticular injectionInflammatory conditionsOA tissuesOsteoarthritis pathophysiologySevere OAIrisinJoint tissuesMouse modelCartilage degradationKnockout miceTherapeutic targetCartilage developmentTherapeutic potential