Correlation of magnetic resonance imaging grades with cytokine levels of synovial fluid of patients with temporomandibular joint disorders: a cross-sectional study

  • Mu-Chen Yang
  • Ding-Han Wang
  • Hung-Ta Wu
  • Wan-Chun Li
  • Tsai-Yu Chang
  • Wen-Liang LoEmail author
  • Ming-Lun HsuEmail author
Original Article



Magnetic resonance imaging (MRI) is a standardized method for assisting joint diagnosis. To validate the reliability of different imaging-based grading systems, this study examined (1) the associations between grading systems for osseous change, joint effusion, and the Wilkes classification of temporomandibular joint (TMJ) disorders and (2) the correlation between cytokines in synovial fluid and imaging-based joint scores.

Materials and methods

Twenty-seven patients, who routinely received numeric rating scale (NRS) and MRI assessment before TMJ arthrocentesis, were enrolled. Each joint was evaluated through the grading criteria for severity of osseous change and joint effusion by blinded observers using MRI. ImageJ was employed for classifying joint effusion. Joint synovial fluid, collected through arthrocentesis, was examined for cytokine expression by using a Luminex multiplex assay. All data were analyzed using the Pearson correlation analysis.


The Wilkes classification was strongly correlated with osseous change scores, but not with joint effusion scores. Joint effusion scores significantly correlated with NRS scores, but not with the Wilkes classification and osseous change scores. Compared with osseous change scores, joint effusion scores had a higher correlation with the levels of inflammatory cytokines (interleukin (IL)-8 and soluble IL-6 receptor (sIL-6R)) and with anti-inflammatory cytokines (soluble tumor necrosis factor receptors I and II (sTNF-RI/II)).


In patients with TMJ disorders, MRI grades are strongly correlated with NRS scores and levels of cytokines (IL-8, sIL-6R, and sTNF-RI/II) in the synovial fluid.

Clinical relevance

Joint effusion scoring can be a reliable and valid indicator for pathological assessment of TMJ disorders.


Temporomandibular joint Magnetic resonance imaging Cytokines Joint effusion 



This research was supported by a grant from the Ministry of Science and Technology, Taiwan (MOST105-2314-B-010-031-MY2).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

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

Supplementary material

784_2019_2817_MOESM1_ESM.pdf (159 kb)
Figure S1 No significant correlation between expression of cytokines and the Wilkes classification. TNF-α, IL-6, IFN-γ, MMP 3, MMP 12, MMP 13, IL-1β, IL-1ra, sIL-1RII, IL-4, IL-10, and IL-13 exhibited no significant correlations with the Wilkes classification. Tumor necrosis factor-α (TNF-α); Interleukin (IL); Interferon (IFN)-γ; Matrix metalloproteinase (MMP); IL-1 receptor antagonist (IL-1ra); Soluble IL-1 receptor II (sIL-1RII). (PDF 158 kb)
784_2019_2817_MOESM2_ESM.pdf (158 kb)
Figure S2 No significant correlation between expression of cytokines and the osseous change score. TNF-α, IL-6, IFN-γ, MMP 3, MMP 12, MMP 13, IL-1β, IL-1ra, sIL-1RII, IL-4, IL-10, and IL-13exhibited no significant correlations with the osseous change score. (PDF 157 kb)
784_2019_2817_MOESM3_ESM.pdf (159 kb)
Figure S3 No significant correlation between expression of cytokines and joint effusion score. TNF-α, IL-6, IFN-γ, MMP 3, MMP 12, MMP 13, IL-1β, IL-1ra, sIL-1RII, IL-4, IL-10, and IL-13 exhibited no significant correlations with the joint effusion score. (PDF 158 kb)


  1. 1.
    Dashnyam K, Lee JH, Mandakhbayar N, Jin GZ, Lee HH, Kim HW (2018) Intra-articular biomaterials-assisted delivery to treat temporomandibular joint disorders. J Tissue Eng 9:2041731418776514CrossRefGoogle Scholar
  2. 2.
    Seifi M, Ebadifar A, Kabiri S, Badiee MR, Abdolazimi Z, Amdjadi P (2017) Comparative effectiveness of low level laser therapy and transcutaneous electric nerve stimulation on temporomandibular joint disorders. J Lasers Med Sci 8:S27–S31CrossRefGoogle Scholar
  3. 3.
    Atsu SS, Ayhan-Ardic F (2006) Temporomandibular disorders seen in rheumatology practices: a review. Rheumatol Int 26:781–787CrossRefGoogle Scholar
  4. 4.
    Shahidi S, Salehi P, Abedi P, Dehbozorgi M, Hamedani S, Berahman N (2018) Comparison of the bony changes of TMJ in patients with and without TMD complaints using CBCT. J Dent (Shiraz) 19:142–149Google Scholar
  5. 5.
    Bristela M, Schmid-Schwap M, Eder J, Reichenberg G, Kundi M, Piehslinger E, Robinson S (2017) Magnetic resonance imaging of temporomandibular joint with anterior disk dislocation without reposition—long-term results. Clin Oral Investig 21:237–245CrossRefGoogle Scholar
  6. 6.
    Larheim TA (2005) Role of magnetic resonance imaging in the clinical diagnosis of the temporomandibular joint. Cells Tissues Organs 180:6–21CrossRefGoogle Scholar
  7. 7.
    Dimitroulis G (2013) A new surgical classification for temporomandibular joint disorders. Int J Oral Maxillofac Surg 42:218–222CrossRefGoogle Scholar
  8. 8.
    Wilkes CH (1989) Internal derangements of the temporomandibular joint. Pathological variations. Arch Otolaryngol Head Neck Surg 115:469–477CrossRefGoogle Scholar
  9. 9.
    Ahmad M, Hollender L, Anderson Q, Kartha K, Ohrbach R, Truelove EL, John MT, Schiffman EL (2009) Research diagnostic criteria for temporomandibular disorders (RDC/TMD): development of image analysis criteria and examiner reliability for image analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107:844–860CrossRefGoogle Scholar
  10. 10.
    Yano K, Sano T, Okano T (2004) A longitudinal study of magnetic resonance (MR) evidence of temporomandibular joint (TMJ) fluid in patients with TMJ disorders. Cranio 22:64–71CrossRefGoogle Scholar
  11. 11.
    Vangsness CT Jr, Burke WS, Narvy SJ, MacPhee RD, Fedenko AN (2011) Human knee synovial fluid cytokines correlated with grade of knee osteoarthritis—a pilot study. Bull NYU Hosp Jt Dis 69:122–127Google Scholar
  12. 12.
    Park HN, Kim KA, Koh KJ (2014) Relationship between pain and effusion on magnetic resonance imaging in temporomandibular disorder patients. Imaging Sci Dent 44:293–299CrossRefGoogle Scholar
  13. 13.
    Swan A, Amer H, Dieppe P (2002) The value of synovial fluid assays in the diagnosis of joint disease: a literature survey. Ann Rheum Dis 61:493–498CrossRefGoogle Scholar
  14. 14.
    Bouloux GF (2009) Temporomandibular joint pain and synovial fluid analysis: a review of the literature. J Oral Maxillofac Surg 67:2497–2504CrossRefGoogle Scholar
  15. 15.
    MIG Campos PC, SRP Line (2006) Inflammatory cytokines activity in temporomandibular joint disorders: a review of literature. Braz J Oral Sci 5:1054–1062Google Scholar
  16. 16.
    Kristensen KD, Alstergren P, Stoustrup P, Kuseler A, Herlin T, Pedersen TK (2014) Cytokines in healthy temporomandibular joint synovial fluid. J Oral Rehabil 41:250–256CrossRefGoogle Scholar
  17. 17.
    Wojdasiewicz P, Poniatowski ŁA, Szukiewicz D (2014) The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediat Inflamm 2014:561459CrossRefGoogle Scholar
  18. 18.
    González-García R (2015) The current role and the future of minimally invasive temporomandibular joint surgery. Oral Maxillofac Surg Clin North Am 27:69–84CrossRefGoogle Scholar
  19. 19.
    Ahmed N, Mustafa HM, Catrina AI, Alstergren P (2013) Impact of temporomandibular joint pain in rheumatoid arthritis. Mediat Inflamm 2013:597419CrossRefGoogle Scholar
  20. 20.
    De Riu G, Stimolo M, Meloni SM et al (2013) Arthrocentesis and temporomandibular joint disorders: clinical and radiological results of a prospective study. Int J Dent 2013:790648Google Scholar
  21. 21.
    Paniagua B, Pascal L, Prieto J, et al (2017) Diagnostic index: an open-source tool to classify TMJ OA condyles. Proc SPIE Int Soc Opt Eng 10137.
  22. 22.
    Al-Hashmi A, Al-Azri A, Al-Ismaily M, Goss AN (2011) Temporomandibular disorders in patients with mandibular fractures: a preliminary comparative case-control study between South Australia and Oman. Int J Oral Maxillofac Surg 40:1369–1372CrossRefGoogle Scholar
  23. 23.
    Suenaga S, Nagayama K, Nagasawa T, Indo H, Majima HJ (2016) The usefulness of diagnostic imaging for the assessment of pain symptoms in temporomandibular disorders. Jpn Dent Sci Rev 52:93–106CrossRefGoogle Scholar
  24. 24.
    Fu KY, Li YW, Zhang ZK, Ma XC (2009) Osteonecrosis of the mandibular condyle as a precursor to osteoarthrosis: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107:e34–e38CrossRefGoogle Scholar
  25. 25.
    Saini A, Saifuddin A (2004) MRI of osteonecrosis. Clin Radiol 59:1079–1093CrossRefGoogle Scholar
  26. 26.
    Larheim TA, Katzberg RW, Westesson PL, Tallents RH, Moss ME (2001) MR evidence of temporomandibular joint fluid and condyle marrow alterations: occurrence in asymptomatic volunteers and symptomatic patients. Int J Oral Maxillofac Surg 30:113–117CrossRefGoogle Scholar
  27. 27.
    Segami N, Nishimura M, Kaneyama K, Miyamaru M, Sato J, Murakami KI (2001) Does joint effusion on T2 magnetic resonance images reflect synovitis? Comparison of arthroscopic findings in internal derangements of the temporomandibular joint. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 92:341–345CrossRefGoogle Scholar
  28. 28.
    Oliveira JX, Rosa JA, Dutra ME, Santos KC, Gil C (2013) Assessing joint effusion and bone changes of the head of the mandible in MR images of symptomatic patients. Braz Oral Res 27:37–41CrossRefGoogle Scholar
  29. 29.
    Nogami S, Takahashi T, Ariyoshi W, Yoshiga D, Morimoto Y, Yamauchi K (2013) Increased levels of interleukin-6 in synovial lavage fluid from patients with mandibular condyle fractures: correlation with magnetic resonance evidence of joint effusion. J Oral Maxillofac Surg 71:1050–1058CrossRefGoogle Scholar
  30. 30.
    Wakita T, Mogi M, Kurita K, Kuzushima M, Togari A (2006) Increase in RANKL: OPG ratio in synovia of patients with temporomandibular joint disorder. J Dent Res 85:627–632CrossRefGoogle Scholar
  31. 31.
    Vernal R, Velásquez E, Gamonal J, Garcia-Sanz JA, Silva A, Sanz M (2008) Expression of proinflammatory cytokines in osteoarthritis of the temporomandibular joint. Arch Oral Biol 53:910–915CrossRefGoogle Scholar
  32. 32.
    Monasterio G, Castillo F, Rojas L et al (2018) Th1/Th17/Th22 immune response and their association with joint pain, imagenological bone loss, RANKL expression and osteoclast activity in temporomandibular joint osteoarthritis: a preliminary report. J Oral Rehabil 45:589–597CrossRefGoogle Scholar
  33. 33.
    Kaneyama K, Segami N, Sun W, Sato J, Fujimura K (2005) Levels of soluble cytokine factors in temporomandibular joint effusions seen on magnetic resonance images. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99:411–418CrossRefGoogle Scholar
  34. 34.
    Kaneyama K, Segami N, Sun W, Sato J, Fujimura K (2005) Analysis of tumor necrosis factor-alpha, interleukin-6, interleukin-1beta, soluble tumor necrosis factor receptors I and II, interleukin-6 soluble receptor, interleukin-1 soluble receptor type II, interleukin-1 receptor antagonist, and protein in the synovial fluid of patients with temporomandibular joint disorders. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99:276–284CrossRefGoogle Scholar
  35. 35.
    Bendre MS, Montague DC, Peery T, Akel NS, Gaddy D, Suva LJ (2003) Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease. Bone 33:28–37CrossRefGoogle Scholar
  36. 36.
    Nishimura M, Segami N, Kaneyama K, Suzuki T, Miyamaru M (2002) Proinflammatory cytokines and arthroscopic findings of patients with internal derangement and osteoarthritis of the temporomandibular joint. Br J Oral Maxillofac Surg 40:68–71CrossRefGoogle Scholar
  37. 37.
    Rose-John S, Scheller J, Elson G, Jones SA (2006) Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J Leukoc Biol 80:227–236CrossRefGoogle Scholar
  38. 38.
    N Ogura TK (2015) Molecular aspects in inflammatory events of temporomandibular joint: microarray-based identification of mediators. Jpn Dent Sci Rev 51:10–24CrossRefGoogle Scholar
  39. 39.
    Walker HK, Hall WD, Hurst JW (1990) Clinical methods: the history, physical, and laboratory examinations, 3rd edn. Butterworths, BostonGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Dentistry, School of DentistryNational Yang-Ming UniversityTaipeiTaiwan
  2. 2.Department of RadiologyTaipei Veterans General HospitalTaipeiTaiwan
  3. 3.Institute of Oral Biology, School of DentistryNational Yang-Ming UniversityTaipeiTaiwan
  4. 4.Cancer Progression CenterNational Yang-Ming UniversityTaipeiTaiwan
  5. 5.Division of Oral and Maxillofacial Surgery, Department of StomatologyTaipei Veterans General HospitalTaipeiTaiwan

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