Featured Publications
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 ResearchMeSH KeywordsCartilage, ArticularChondrocytesCohort StudiesDigoxinDrug RepositioningHumansLDL-Receptor Related ProteinsOsteoarthritisOuabainConceptsLow-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 stimulator14-3-3 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 protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling
Zhao Y, Liu B, Tian Q, Wei J, Richbourgh B, Liu C. Progranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling. Annals Of The Rheumatic Diseases 2014, 74: 2244. PMID: 25169730, PMCID: PMC4408266, DOI: 10.1136/annrheumdis-2014-205779.Peer-Reviewed Original ResearchConceptsPGRN-deficient miceProgression of OAOA modelTumor necrosis factor αMechanism of progranulinRecombinant PGRN proteinArthritis mouse modelOA-like phenotypeRole of progranulinNecrosis factor αPathogenesis of OAJoint degenerative diseaseTNF receptor 2Degradation of cartilageExtracellular signal-regulated kinase 1/2Signal-regulated kinase 1/2Β-catenin signalingInflammatory actionsOA progressionAnabolic biomarkersAnabolic effectsOA developmentSafranin O stainingTherapeutic roleMouse modelThe Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice
Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, Syed NM, Lai Y, Lin EA, Kong L, Su J, Yin F, Ding AH, Zanin-Zhorov A, Dustin ML, Tao J, Craft J, Yin Z, Feng JQ, Abramson SB, Yu XP, Liu CJ. The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice. Science 2011, 332: 478-484. PMID: 21393509, PMCID: PMC3104397, DOI: 10.1126/science.1199214.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnimalsAnti-Inflammatory Agents, Non-SteroidalArthritis, ExperimentalCartilage, ArticularFemaleGranulinsHumansIntercellular Signaling Peptides and ProteinsLigandsMaleMiceMice, Inbred StrainsMice, KnockoutMice, TransgenicMiddle AgedProgranulinsProtein Interaction Domains and MotifsReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IIRecombinant Fusion ProteinsRecombinant ProteinsSignal TransductionT-Lymphocytes, RegulatoryTumor Necrosis Factor-alphaYoung AdultConceptsInflammatory arthritisAdministration of progranulinAntagonist of TNFαCollagen-induced arthritisArthritis mouse modelPGRN-deficient miceNew potential therapeutic interventionsPotential therapeutic interventionsGrowth factor progranulinNecrosis factor receptorRheumatoid arthritisMouse modelArthritisTherapeutic interventionsProgranulinTNF receptorFactor receptorMiceReceptorsInflammationTissue repairTNFαIntracellular signalingAtsttrinTNFR
2022
Injectable 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 ResearchMeSH KeywordsAnimalsAnterior Cruciate Ligament InjuriesBiocompatible MaterialsCartilage, ArticularGelsOsteoarthritisPolymersProgranulinsRabbitsConceptsUnique 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) model
2018
Role of ADAMTS‐12 in Protecting Against Inflammatory Arthritis in Mice By Interacting With and Inactivating Proinflammatory Connective Tissue Growth Factor
Wei J, Fu W, Hettinghouse A, He W, Lipson K, Liu C. Role of ADAMTS‐12 in Protecting Against Inflammatory Arthritis in Mice By Interacting With and Inactivating Proinflammatory Connective Tissue Growth Factor. Arthritis & Rheumatology 2018, 70: 1745-1756. PMID: 29750395, PMCID: PMC6203634, DOI: 10.1002/art.40552.Peer-Reviewed Original ResearchConceptsConnective tissue growth factorCIA mouse modelADAMTS-12Inflammatory arthritisTissue growth factorMouse modelCollagen-induced arthritis modelGrowth factorRheumatoid arthritis developmentEnzyme-linked immunosorbentRA patientsArthritis developmentPannus formationSerum levelsCartilage destructionArthritis modelInflammatory cytokinesEnhanced osteoclastogenesisHealthy subjectsArthritisAnkle jointTomography scanningInflammationSusceptibility genesCritical regulator
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
2016
Chondro-protective effects of low intensity pulsed ultrasound
Uddin S, Richbourgh B, Ding Y, Hettinghouse A, Komatsu D, Qin Y, Liu C. Chondro-protective effects of low intensity pulsed ultrasound. Osteoarthritis And Cartilage 2016, 24: 1989-1998. PMID: 27364595, PMCID: PMC5071131, DOI: 10.1016/j.joca.2016.06.014.Peer-Reviewed Original ResearchMeSH KeywordsCartilage, ArticularCells, CulturedChondrocytesHumansInterleukin-1betaOsteoarthritisUltrasonic WavesConceptsIL-1βHuman cartilage explantsCartilage degradationMesenchymal stem cellsIL-1β induced activationPotential therapeutic effectsChondro-protective effectsPathogenesis of osteoarthritisLIPUS stimulationCartilage explantsChondrocyte migrationWestern blot analysisLoss of proteoglycanTherapeutic effectNFκB p65Catabolic actionMetabolic alterationsNFκB pathwayOsteoarthritisReduced expressionChondrocyte metabolismInduced activationMechanical stimulationLIPUSStimulation
2011
Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2
Du Y, Wang Y, Wang L, Liu B, Tian Q, Liu C, Zhang T, Xu Q, Zhu Y, Ake O, Qi Y, Tang C, Kong W, Wang X. Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2. Circulation Research 2011, 108: 917-928. PMID: 21350216, DOI: 10.1161/circresaha.110.234328.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsCartilage oligomeric matrix proteinVascular calcificationOligomeric matrix proteinVSMC calcificationVascular smooth muscle calcificationMarker expressionHigh-phosphate dietSmooth muscle cellsCOMP deficiencyMuscle calcificationCardiovascular morbidityOsteogenic marker expressionAbdominal aortaVessel calcificationHigh inorganic phosphateEffects of COMPPeriadventitial applicationMatrix proteinsMuscle cellsCalcificationBMP-2Receptor bindingProtein levelsOsteogenic signaling