Synovial tissue cytokine profile in disc displacement of the temporomandibular joint

Abstract

Background Symptomatic disc displacement (DD) of the temporomandibular joint (TMJ) may cause pain and limited mouth opening. The aetiopathogenesis is obscure and probably complex, which makes the diagnostic classification crude and mainly based on clinical criteria rather than disease mechanisms, and tissue characteristics. Objectives The study aim was to characterise and quantify synovial tissue in DD, where specific cytokine patterns might serve as potential biomarkers. Methods An observational cohort study was performed harvesting synovial tissue from 63 patients: 44 with DD without reduction (DDwoR) and 19 with DD with reduction (DDwR). DDwoR was subdivided depending on type of onset (sudden, n = 17; delayed, n = 27), and DDwR served as the control group. Proteins were extracted from tissue samples and investigated in a multi‐analytic profiling system. Results DDwoR patients had significantly higher concentrations in 12 out of 28 analysed cytokines compared to DDwR. In the same statistical model, significantly lower concentrations of interferon gamma‐induced protein (IP) 10, osteoprotegerin (OPG) and RANTES were detected in DDwoR patients. Women showed significantly higher concentrations of epidermal growth factor and interleukin (IL) 1ra compared to men. DDwoR with sudden onset had significant higher concentrations of bone morphogenetic protein 4, eotaxin and IL‐8 compared to DDwoR with delayed onset. Conclusions Characterising the biomarker panel for TMJ conditions may serve as suggestible targets for disease classification and novel treatment options. The significantly lower concentrations of IP‐10, OPG and RANTES could be proposed as putative markers for the separation of the studied conditions to other TMJ diseases.

Preclinical models of deep craniofacial nociception and temporomandibular disorder pain

“…For example, local injection of cytokines [ 30 ], glutamate [ [35] , [36] , [37] , [38] ], serotonin [ 39 ], acid saline [ 40 ] and nerve growth factor [ 41 , 42 ] can cause pain and hyperalgesia in the deep craniofacial tissues. These results are consistent with the findings that TMD patients increase experimentally-induced pain sensitivity in the facial areas, in which the level of inflammatory mediators is elevated [ 24 , [27] , [28] , [29] , [30] , [31] , [32] , [33] , 43 , 44 ].…”

“…Proinflammatory mediators affect nociception in the deep craniofacial tissues. Cytokines such as interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha are identified in the synovial fluid of the TMJ in TMD patients [ [25] , [26] , [27] ], whereas those are not detected in the healthy controls [ 26 ]. Painful TMD with disk displacement (DD) without reduction displays higher levels of IL-1 beta, TNF-alpha and TNF-beta in the TMJ compared with that with DD with reduction [ 27 ].…”

“…Cytokines such as interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha are identified in the synovial fluid of the TMJ in TMD patients [ [25] , [26] , [27] ], whereas those are not detected in the healthy controls [ 26 ]. Painful TMD with disk displacement (DD) without reduction displays higher levels of IL-1 beta, TNF-alpha and TNF-beta in the TMJ compared with that with DD with reduction [ 27 ]. TMD patients suffering from osteoarthritis show a higher level of IL-1 beta in synovial fluids [ 22 , 26 , 27 ]; however, most cytokines except IL-1 beta are less correlated with pain [ 26 ].…”

“…Painful TMD with disk displacement (DD) without reduction displays higher levels of IL-1 beta, TNF-alpha and TNF-beta in the TMJ compared with that with DD with reduction [ 27 ]. TMD patients suffering from osteoarthritis show a higher level of IL-1 beta in synovial fluids [ 22 , 26 , 27 ]; however, most cytokines except IL-1 beta are less correlated with pain [ 26 ]. IL-1 beta has been reported to play critical roles on the development and progression of TMD pain [ 22 , 24 ].…”

Oxygen-Ozone Therapy for Reducing Pro-Inflammatory Cytokines Serum Levels in Musculoskeletal and Temporomandibular Disorders: A Comprehensive Review

“…More in detail, both immune and non-immune cells could release TNF-α (e.g., macrophages, synoviocytes, and neurons associated with the trigeminal ganglion), causing TMJ inflammation and pain in myofascial TMD patients [ 165 ]. Ulmner et al [ 166 ] characterized and quantified the synovial tissue cytokines and related the result to the diagnoses of disc displacement with or without reduction. Results of this study showed that bone morphogenetic protein (BMP) type 2 and 4, epidermal growth factor (EGF), eotaxin, granulocyte-colony stimulating factor (G-CSF), IL-1β, IL-7, IL-8, IL-10, macrophage inflammatory protein (MIP) 1β, TNF-α and TNF-β had significantly higher concentrations in patients with disc displacement without reduction.…”