Synovial fluid-derived exosomal lncRNA PCGEM1 as biomarker for the different stages of osteoarthritis



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.

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  1. 1.

    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).

  2. 2.

    Rahmati M, Nalesso G, Mobasheri A, Mozafari M (2017) Aging and osteoarthritis: central role of the extracellular matrix. Ageing Res Rev 40:20–30

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Flemming DJ, Gustas-French CN (2017) Rapidly progressive osteoarthritis: a review of the clinical and radiologic presentation. Curr Rheumatol Rep 19:42

    Article  PubMed  Google Scholar 

  4. 4.

    Shang X, Wang Z, Tao H (2017) Mechanism and therapeutic effectiveness of nerve growth factor in osteoarthritis pain. Ther Clin Risk Manag 13:951–956

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Azamar-Llamas D, Hernandez-Molina G, Ramos-Avalos B, Furuzawa-Carballeda J (2017) Adipokine contribution to the pathogenesis of osteoarthritis. Mediat Inflamm 2017:5468023

    Article  CAS  Google Scholar 

  6. 6.

    Jorgensen AEM, Kjaer M, Heinemeier KM (2017) The effect of aging and mechanical loading on the metabolism of articular cartilage. J Rheumatol 44:410–417

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    Kolhe R, Hunter M, Liu S, Jadeja RN, Pundkar C, Mondal AK, Mendhe B, Drewry M, Rojiani MV, Liu Y, Isales CM, Guldberg RE, Hamrick MW, Fulzele S (2017) Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis. Sci Rep 7:2029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Blackwell RH, Foreman KE, Gupta GN (2017) The role of Cancer-derived exosomes in tumorigenicity & epithelial-to-mesenchymal transition. Cancers 9:105–115

    Article  CAS  PubMed Central  Google Scholar 

  9. 9.

    Moris D, Beal EW, Chakedis J, Burkhart RA, Schmidt C, Dillhoff M, Zhang X, Theocharis S, Pawlik TM (2017) Role of exosomes in treatment of hepatocellular carcinoma. Surg Oncol 26:219–228

    Article  PubMed  Google Scholar 

  10. 10.

    Silva A, Bullock M, Calin G (2015) The clinical relevance of long non-coding RNAs in cancer. Cancers 7:2169–2182

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Liu Q, Zhang X, Dai L, Hu X, Zhu J, Li L, Zhou C, Ao Y (2014) Long noncoding RNA related to cartilage injury promotes chondrocyte extracellular matrix degradation in osteoarthritis. Arthritis Rheum 66:969–978

    CAS  Article  Google Scholar 

  12. 12.

    Jiang SD, Lu J, Deng ZH, Li YS, Lei GH (2016) Long noncoding RNAs in osteoarthritis. Joint Bone Spine 84: 553–556

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Liu T, Zhang X, Gao S, Jing F, Yang Y, Du L, Zheng G, Li P, Li C, Wang C (2016) Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer. Oncotarget 7:85551–85563

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Dong L, Lin W, Qi P, Xu MD, Wu X, Ni S, Huang D, Weng WW, Tan C, Sheng W, Zhou X, Du X (2016) Circulating long RNAs in serum extracellular vesicles: their characterization and potential application as biomarkers for diagnosis of colorectal Cancer. Cancer Epidemiol Biomark Prev 25:1158–1166

    CAS  Article  Google Scholar 

  15. 15.

    Song J, Ahn C, Chun CH, Jin EJ (2014) A long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritis. J Orthop Res 32:1628–1635

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Kang Y, Song J, Kim D, Ahn C, Park S, Chun CH, Jin EJ (2016) PCGEM1 stimulates proliferation of osteoarthritic synoviocytes by acting as a sponge for miR-770. J Orthop Res 34:412–418

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Zhang C, Wang P, Jiang P, Lv Y, Dong C, Dai X, Tan L, Wang Z (2016) Upregulation of lncRNA HOTAIR contributes to IL-1beta-induced MMP overexpression and chondrocytes apoptosis in temporomandibular joint osteoarthritis. Gene 586:248–253

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Zhang A, Zhao JC, Kim J, Fong KW, Yang YA, Chakravarti D, Mo YY, Yu J (2015) LncRNA HOTAIR enhances the androgen-receptor-mediated transcriptional program and drives castration-resistant prostate cancer. Cell Rep 13:209–221

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Zhang Z, Zhou N, Huang J, Ho TT, Zhu Z, Qiu Z, Zhou X, Bai C, Wu F, Xu M, Mo YY (2016) Regulation of androgen receptor splice variant AR3 by PCGEM1. Oncotarget 7:15481–15491

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Chen L, Yang H, Xiao Y, Tang X, Li Y, Han Q, Fu J, Yang Y, Zhu Y (2016) LncRNA GAS5 is a critical regulator of metastasis phenotype of melanoma cells and inhibits tumor growth in vivo. OncoTargets Ther 9:4075–4087

    CAS  Article  Google Scholar 

  22. 22.

    Chu CR, Williams AA, Coyle CH, Bowers ME (2012) Early diagnosis to enable early treatment of pre-osteoarthritis. Arthritis Res Ther 14:212

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, Laslett LL, Jones G, Cicuttini F, Osborne R, Vos T, Buchbinder R, Woolf A, March L (2014) The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 73:1323–1330

    Article  PubMed  Google Scholar 

  24. 24.

    Martel-Pelletier J, Barr AJ, Cicuttini FM, Conaghan PG, Cooper C, Goldring MB, Goldring SR, Jones G, Teichtahl AJ, Pelletier JP (2016) Osteoarthritis. Nat Rev Dis Primers 2:16072

    Article  PubMed  Google Scholar 

  25. 25.

    Dong T, Chang H, Zhang F, Chen W, Zhu Y, Wu T, Zhang Y (2015) Calcitonin gene-related peptide can be selected as a predictive biomarker on progression and prognosis of knee osteoarthritis. Int Orthop 39:1237–1243

    Article  PubMed  Google Scholar 

  26. 26.

    Mabey T, Honsawek S, Saetan N, Poovorawan Y, Tanavalee A, Yuktanandana P (2014) Angiogenic cytokine expression profiles in plasma and synovial fluid of primary knee osteoarthritis. Int Orthop 38:1885–1892

    Article  PubMed  Google Scholar 

  27. 27.

    Lipina M, Makarov M, Makarov S, Novikov A (2017) The degree of cartilage degradation assessed by serum biomarker levels changes after arthroscopic knee synovectomy in rheumatoid arthritis patients. Int Orthop 41:1–6

    Article  Google Scholar 

  28. 28.

    Prensner JR, Sahu A, Iyer MK, Malik R, Chandler B, Asangani IA, Poliakov A, Vergara IA, Alshalalfa M, Jenkins RB (2014) The IncRNAs PCGEM1 and PRNCR1 are not implicated in castration resistant prostate cancer. Oncotarget 5:1434–1438

    Article  PubMed  PubMed Central  Google Scholar 

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This work was supported by the Hebei Science and Technology Science and Technology Support Program (1123038ZD).

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Correspondence to Ye Zhao.

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The authors declare that they have no conflict of interest.

Ethical approval

Ethical approval was approved by the Ethics Committee of Cangzhou Central Hospital.

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Informed consent was obtained from all individual participants included in the study.

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Zhao, Y., Xu, J. Synovial fluid-derived exosomal lncRNA PCGEM1 as biomarker for the different stages of osteoarthritis. International Orthopaedics (SICOT) 42, 2865–2872 (2018).

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  • lncRNA
  • Osteoarthritis
  • Exosomes