Synovial fluid-derived exosomal lncRNA PCGEM1 as biomarker for the different stages of osteoarthritis
Objects The purpose of this study is to investigate the role of exosomal lncRNAs from plasma and from synovial fluid in patients with osteoarthritis (OA) and to determine their diagnostic value in distinguishing the early stage of OA from progressive stage of OA. Methods Participants were divided in...
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Published in | International orthopaedics Vol. 42; no. 12; pp. 2865 - 2872 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.12.2018
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Subjects | |
Online Access | Get full text |
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Abstract | Objects
The purpose of this study is to investigate the role of exosomal lncRNAs from plasma and from synovial fluid in patients with osteoarthritis (OA) and to determine their diagnostic value in distinguishing the early stage of OA from progressive stage of OA.
Methods
Participants were divided into three groups. The control group included 20 pre-arthritic patients, early OA group included 20 patients in the early OA, and late-stage OA group included 22 patients in the late-stage OA. For all subjects, blood sample from cubital vein and synovial fluid sample from knee joint were collected. Exosomes were extracted by ultracentrifugation. LncRNAs were extracted from exosomes using RNeasy kit, and the expression of several exosomal lncRNAs, including HOTAIR, PCGEM1, and GAS5, was measured using quantitative real-time polymerase chain reaction (qPCR). Also, Spearman’s correlation test was performed to determine the correlation between exosomal lncRNA PCGEM1 and WOMAC index. Last, the receiver operating characteristic (ROC) curve was performed to determine the diagnostic value of exosomal lncRNA PCGEM1 in distinguishing the different stages of OA.
Results
First, for plasma, both the expression of exosomes in three groups and the relative expression of exosomal lncRNAs chosen showed no significant difference among three groups, while for synovial fluid sample, the expression of exosomes in early OA and late-stage OA was much markedly higher than that in controls; and the expression of exosomal lncRNA PCGEM1 was markedly higher in late-stage OA than in early OA, and markedly higher in early OA than controls. Both the expression of exosomal lncRNA HOTAIR and GAS5 showed no significant difference among these groups. Second, there was a positive relationship between exosomal lncRNA PCGEM1 and WOMAC Index. Last, ROC curve showed that the area values under the curve of exosomal lncRNA PCGEM1 were 0.879, 0.757, and 0.593, respectively.
Conclusion
Our study demonstrated that exosomal lncRNA PCGEM1 might be a powerful indicator in distinguishing the early OA from the late-stage OA. |
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AbstractList | The purpose of this study is to investigate the role of exosomal lncRNAs from plasma and from synovial fluid in patients with osteoarthritis (OA) and to determine their diagnostic value in distinguishing the early stage of OA from progressive stage of OA.
Participants were divided into three groups. The control group included 20 pre-arthritic patients, early OA group included 20 patients in the early OA, and late-stage OA group included 22 patients in the late-stage OA. For all subjects, blood sample from cubital vein and synovial fluid sample from knee joint were collected. Exosomes were extracted by ultracentrifugation. LncRNAs were extracted from exosomes using RNeasy kit, and the expression of several exosomal lncRNAs, including HOTAIR, PCGEM1, and GAS5, was measured using quantitative real-time polymerase chain reaction (qPCR). Also, Spearman's correlation test was performed to determine the correlation between exosomal lncRNA PCGEM1 and WOMAC index. Last, the receiver operating characteristic (ROC) curve was performed to determine the diagnostic value of exosomal lncRNA PCGEM1 in distinguishing the different stages of OA.
First, for plasma, both the expression of exosomes in three groups and the relative expression of exosomal lncRNAs chosen showed no significant difference among three groups, while for synovial fluid sample, the expression of exosomes in early OA and late-stage OA was much markedly higher than that in controls; and the expression of exosomal lncRNA PCGEM1 was markedly higher in late-stage OA than in early OA, and markedly higher in early OA than controls. Both the expression of exosomal lncRNA HOTAIR and GAS5 showed no significant difference among these groups. Second, there was a positive relationship between exosomal lncRNA PCGEM1 and WOMAC Index. Last, ROC curve showed that the area values under the curve of exosomal lncRNA PCGEM1 were 0.879, 0.757, and 0.593, respectively.
Our study demonstrated that exosomal lncRNA PCGEM1 might be a powerful indicator in distinguishing the early OA from the late-stage OA. Objects The purpose of this study is to investigate the role of exosomal lncRNAs from plasma and from synovial fluid in patients with osteoarthritis (OA) and to determine their diagnostic value in distinguishing the early stage of OA from progressive stage of OA. Methods Participants were divided into three groups. The control group included 20 pre-arthritic patients, early OA group included 20 patients in the early OA, and late-stage OA group included 22 patients in the late-stage OA. For all subjects, blood sample from cubital vein and synovial fluid sample from knee joint were collected. Exosomes were extracted by ultracentrifugation. LncRNAs were extracted from exosomes using RNeasy kit, and the expression of several exosomal lncRNAs, including HOTAIR, PCGEM1, and GAS5, was measured using quantitative real-time polymerase chain reaction (qPCR). Also, Spearman’s correlation test was performed to determine the correlation between exosomal lncRNA PCGEM1 and WOMAC index. Last, the receiver operating characteristic (ROC) curve was performed to determine the diagnostic value of exosomal lncRNA PCGEM1 in distinguishing the different stages of OA. Results First, for plasma, both the expression of exosomes in three groups and the relative expression of exosomal lncRNAs chosen showed no significant difference among three groups, while for synovial fluid sample, the expression of exosomes in early OA and late-stage OA was much markedly higher than that in controls; and the expression of exosomal lncRNA PCGEM1 was markedly higher in late-stage OA than in early OA, and markedly higher in early OA than controls. Both the expression of exosomal lncRNA HOTAIR and GAS5 showed no significant difference among these groups. Second, there was a positive relationship between exosomal lncRNA PCGEM1 and WOMAC Index. Last, ROC curve showed that the area values under the curve of exosomal lncRNA PCGEM1 were 0.879, 0.757, and 0.593, respectively. Conclusion Our study demonstrated that exosomal lncRNA PCGEM1 might be a powerful indicator in distinguishing the early OA from the late-stage OA. The purpose of this study is to investigate the role of exosomal lncRNAs from plasma and from synovial fluid in patients with osteoarthritis (OA) and to determine their diagnostic value in distinguishing the early stage of OA from progressive stage of OA.OBJECTSThe purpose of this study is to investigate the role of exosomal lncRNAs from plasma and from synovial fluid in patients with osteoarthritis (OA) and to determine their diagnostic value in distinguishing the early stage of OA from progressive stage of OA.Participants were divided into three groups. The control group included 20 pre-arthritic patients, early OA group included 20 patients in the early OA, and late-stage OA group included 22 patients in the late-stage OA. For all subjects, blood sample from cubital vein and synovial fluid sample from knee joint were collected. Exosomes were extracted by ultracentrifugation. LncRNAs were extracted from exosomes using RNeasy kit, and the expression of several exosomal lncRNAs, including HOTAIR, PCGEM1, and GAS5, was measured using quantitative real-time polymerase chain reaction (qPCR). Also, Spearman's correlation test was performed to determine the correlation between exosomal lncRNA PCGEM1 and WOMAC index. Last, the receiver operating characteristic (ROC) curve was performed to determine the diagnostic value of exosomal lncRNA PCGEM1 in distinguishing the different stages of OA.METHODSParticipants were divided into three groups. The control group included 20 pre-arthritic patients, early OA group included 20 patients in the early OA, and late-stage OA group included 22 patients in the late-stage OA. For all subjects, blood sample from cubital vein and synovial fluid sample from knee joint were collected. Exosomes were extracted by ultracentrifugation. LncRNAs were extracted from exosomes using RNeasy kit, and the expression of several exosomal lncRNAs, including HOTAIR, PCGEM1, and GAS5, was measured using quantitative real-time polymerase chain reaction (qPCR). Also, Spearman's correlation test was performed to determine the correlation between exosomal lncRNA PCGEM1 and WOMAC index. Last, the receiver operating characteristic (ROC) curve was performed to determine the diagnostic value of exosomal lncRNA PCGEM1 in distinguishing the different stages of OA.First, for plasma, both the expression of exosomes in three groups and the relative expression of exosomal lncRNAs chosen showed no significant difference among three groups, while for synovial fluid sample, the expression of exosomes in early OA and late-stage OA was much markedly higher than that in controls; and the expression of exosomal lncRNA PCGEM1 was markedly higher in late-stage OA than in early OA, and markedly higher in early OA than controls. Both the expression of exosomal lncRNA HOTAIR and GAS5 showed no significant difference among these groups. Second, there was a positive relationship between exosomal lncRNA PCGEM1 and WOMAC Index. Last, ROC curve showed that the area values under the curve of exosomal lncRNA PCGEM1 were 0.879, 0.757, and 0.593, respectively.RESULTSFirst, for plasma, both the expression of exosomes in three groups and the relative expression of exosomal lncRNAs chosen showed no significant difference among three groups, while for synovial fluid sample, the expression of exosomes in early OA and late-stage OA was much markedly higher than that in controls; and the expression of exosomal lncRNA PCGEM1 was markedly higher in late-stage OA than in early OA, and markedly higher in early OA than controls. Both the expression of exosomal lncRNA HOTAIR and GAS5 showed no significant difference among these groups. Second, there was a positive relationship between exosomal lncRNA PCGEM1 and WOMAC Index. Last, ROC curve showed that the area values under the curve of exosomal lncRNA PCGEM1 were 0.879, 0.757, and 0.593, respectively.Our study demonstrated that exosomal lncRNA PCGEM1 might be a powerful indicator in distinguishing the early OA from the late-stage OA.CONCLUSIONOur study demonstrated that exosomal lncRNA PCGEM1 might be a powerful indicator in distinguishing the early OA from the late-stage OA. |
Author | Zhao, Ye Xu, Juan |
Author_xml | – sequence: 1 givenname: Ye surname: Zhao fullname: Zhao, Ye email: zhaoyeczcp@163.com organization: Department of Orthopedics, Cangzhou Central Hospital – sequence: 2 givenname: Juan surname: Xu fullname: Xu, Juan organization: Department of Ultrasound, Cangzhou Central Hospital |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30128669$$D View this record in MEDLINE/PubMed |
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References_xml | – reference: ShangXWangZTaoHMechanism and therapeutic effectiveness of nerve growth factor in osteoarthritis painTher Clin Risk Manag20171395195610.2147/TCRM.S139814288148775546917 – reference: FlemmingDJGustas-FrenchCNRapidly progressive osteoarthritis: a review of the clinical and radiologic presentationCurr Rheumatol Rep2017194210.1007/s11926-017-0665-528689367 – reference: DongLLinWQiPXuMDWuXNiSHuangDWengWWTanCShengWZhouXDuXCirculating long RNAs in serum extracellular vesicles: their characterization and potential application as biomarkers for diagnosis of colorectal CancerCancer Epidemiol Biomark Prev201625115811661:CAS:528:DC%2BC28XhtVyitLvI10.1158/1055-9965.EPI-16-0006 – reference: ChenLYangHXiaoYTangXLiYHanQFuJYangYZhuYLncRNA GAS5 is a critical regulator of metastasis phenotype of melanoma cells and inhibits tumor growth in vivoOncoTargets Ther20169407540871:CAS:528:DC%2BC1cXnsFyjtL4%3D10.2147/OTT.S98203 – reference: ChuCRWilliamsAACoyleCHBowersMEEarly diagnosis to enable early treatment of pre-osteoarthritisArthritis Res Ther20121421210.1186/ar3845226824693446496 – reference: SilvaABullockMCalinGThe clinical relevance of long non-coding RNAs in cancerCancers20157216921821:CAS:528:DC%2BC1cXlslGju7c%3D10.3390/cancers7040884265169184695884 – reference: ZhangAZhaoJCKimJFongKWYangYAChakravartiDMoYYYuJLncRNA HOTAIR enhances the androgen-receptor-mediated transcriptional program and drives castration-resistant prostate cancerCell Rep2015132092211:CAS:528:DC%2BC2MXhsFKqsbvE10.1016/j.celrep.2015.08.069264116894757469 – reference: LiuQZhangXDaiLHuXZhuJLiLZhouCAoYLong noncoding RNA related to cartilage injury promotes chondrocyte extracellular matrix degradation in osteoarthritisArthritis Rheum2014669699781:CAS:528:DC%2BC2cXhtl2qtbfE10.1002/art.38309 – reference: DongTChangHZhangFChenWZhuYWuTZhangYCalcitonin gene-related peptide can be selected as a predictive biomarker on progression and prognosis of knee osteoarthritisInt Orthop2015391237124310.1007/s00264-015-2744-425813459 – reference: ZhangCWangPJiangPLvYDongCDaiXTanLWangZUpregulation of lncRNA HOTAIR contributes to IL-1beta-induced MMP overexpression and chondrocytes apoptosis in temporomandibular joint osteoarthritisGene20165862482531:CAS:528:DC%2BC28Xms1OlsLs%3D10.1016/j.gene.2016.04.01627063559 – reference: JorgensenAEMKjaerMHeinemeierKMThe effect of aging and mechanical loading on the metabolism of articular cartilageJ Rheumatol20174441041710.3899/jrheum.1602261:CAS:528:DC%2BC1cXmsV2nsL8%3D28250141 – reference: RahmatiMNalessoGMobasheriAMozafariMAging and osteoarthritis: central role of the extracellular matrixAgeing Res Rev20174020301:CAS:528:DC%2BC2sXhtlartLzI10.1016/j.arr.2017.07.00428774716 – reference: KangYSongJKimDAhnCParkSChunCHJinEJPCGEM1 stimulates proliferation of osteoarthritic synoviocytes by acting as a sponge for miR-770J Orthop Res2016344124181:CAS:528:DC%2BC28XjsFaqsL0%3D10.1002/jor.2304626340084 – reference: PrensnerJRSahuAIyerMKMalikRChandlerBAsanganiIAPoliakovAVergaraIAAlshalalfaMJenkinsRBThe IncRNAs PCGEM1 and PRNCR1 are not implicated in castration resistant prostate cancerOncotarget201451434143810.18632/oncotarget.1846247277384039221 – reference: ZhangZZhouNHuangJHoTTZhuZQiuZZhouXBaiCWuFXuMMoYYRegulation of androgen receptor splice variant AR3 by PCGEM1Oncotarget201671548115491268488684941255 – reference: CrossMSmithEHoyDNolteSAckermanIFransenMBridgettLWilliamsSGuilleminFHillCLLaslettLLJonesGCicuttiniFOsborneRVosTBuchbinderRWoolfAMarchLThe global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 studyAnn Rheum Dis2014731323133010.1136/annrheumdis-2013-20476324553908 – reference: LiuTZhangXGaoSJingFYangYDuLZhengGLiPLiCWangCExosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancerOncotarget201678555185563278888035356757 – reference: Martel-PelletierJBarrAJCicuttiniFMConaghanPGCooperCGoldringMBGoldringSRJonesGTeichtahlAJPelletierJPOsteoarthritisNat Rev Dis Primers201621607210.1038/nrdp.2016.7227734845 – reference: Newberry SJ, FitzGerald J, SooHoo NF, Booth M, Marks J, Motala A, Apaydin E, Chen C, Raaen L, Shanman R, Shekelle PG (2017) Treatment of osteoarthritis of the knee: an update review. Rockville (MD). https://www.ncbi.nlm.nih.gov/pubmed/28825779 – reference: SongJAhnCChunCHJinEJA long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritisJ Orthop Res201432162816351:CAS:528:DC%2BC2cXhslOlu7rO10.1002/jor.2271825196583 – reference: MabeyTHonsawekSSaetanNPoovorawanYTanavaleeAYuktanandanaPAngiogenic cytokine expression profiles in plasma and synovial fluid of primary knee osteoarthritisInt Orthop2014381885189210.1007/s00264-014-2406-y24966080 – reference: KolheRHunterMLiuSJadejaRNPundkarCMondalAKMendheBDrewryMRojianiMVLiuYIsalesCMGuldbergREHamrickMWFulzeleSGender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritisSci Rep20177202910.1038/s41598-017-01905-y1:CAS:528:DC%2BC2sXhslGlu7rI285154655435729 – reference: JiangSDLuJDengZHLiYSLeiGHLong noncoding RNAs in osteoarthritisJoint Bone Spine20168455355610.1016/j.jbspin.2016.09.0061:CAS:528:DC%2BC28XhsFOmsb7O27919571 – reference: KellgrenJHLawrenceJSRadiological assessment of osteo-arthrosisAnn Rheum Dis1957164941:STN:280:DyaG1c%2FktFeltQ%3D%3D10.1136/ard.16.4.49410069951006995 – reference: Azamar-LlamasDHernandez-MolinaGRamos-AvalosBFuruzawa-CarballedaJAdipokine contribution to the pathogenesis of osteoarthritisMediat Inflamm20172017546802310.1155/2017/54680231:CAS:528:DC%2BC1cXkvVartrs%3D – reference: BlackwellRHForemanKEGuptaGNThe role of Cancer-derived exosomes in tumorigenicity & epithelial-to-mesenchymal transitionCancers2017910511510.3390/cancers90801051:CAS:528:DC%2BC1cXisVGrtLbM5575608 – reference: MorisDBealEWChakedisJBurkhartRASchmidtCDillhoffMZhangXTheocharisSPawlikTMRole of exosomes in treatment of hepatocellular carcinomaSurg Oncol20172621922810.1016/j.suronc.2017.04.00528807240 – reference: LipinaMMakarovMMakarovSNovikovAThe degree of cartilage degradation assessed by serum biomarker levels changes after arthroscopic knee synovectomy in rheumatoid arthritis patientsInt Orthop2017411610.1007/s00264-017-3634-8 |
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The purpose of this study is to investigate the role of exosomal lncRNAs from plasma and from synovial fluid in patients with osteoarthritis (OA) and... The purpose of this study is to investigate the role of exosomal lncRNAs from plasma and from synovial fluid in patients with osteoarthritis (OA) and to... |
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SubjectTerms | Biomarkers - metabolism Exosomes Humans Medicine Medicine & Public Health Original Paper Orthopedics Osteoarthritis - diagnosis Osteoarthritis - genetics Osteoarthritis - metabolism RNA, Long Noncoding - genetics RNA, Long Noncoding - metabolism ROC Curve Synovial Fluid - metabolism |
Title | Synovial fluid-derived exosomal lncRNA PCGEM1 as biomarker for the different stages of osteoarthritis |
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