Elastin-derived Peptides Induce Inflammatory Responses in Synovial Cells of Human Temporomandibular Joint

Intracapsular pathologic conditions of the temporomandibular joint (TMJ) are characterized by limited jaw motion, joint sound and pain, and can include disk displacement and osteoarthritis (OA). Synovitis that often accompanies intracapsular pathologic conditions is characterized by chronic inflammatory changes. The synovial membrane covers the inner wall of the TMJ capsule and is populated by stromal cells and lining cells, which are both fibroblast-like. It is accepted that fibroblast-like synovial cells play a key role in the progression of inflammation in TMJ because of their ability to produce a number of putative mediators of inflammation. Elastin is the extracellular matrix molecule responsible for resilience of tissues and was first thought to be restricted to that role. Recently, it is established that elastin-derived peptides (EDPs) from breakdown of elastic fibers display a wide range of biological activities in a variety of cells (1). Specific interactions between inflammatory cells and EDPs and cancer cells and EDPs, respectively, have been known for a long time (2). But there is minimal information regarding the involvement of EDPs in the processes of synovitis in human temporomandibular disorder (TMD). The present work aims to elucidate the effects of EDPs in TMD and to investigate the molecular and biochemical mechanisms by which EDPs induce temporomandibular disorder. First of all, the level of EDPs in TMJ fluid of TMD patients was examined. Sandwich enzyme immunoassays revealed that EDPs levels significantly correlated with the VAS scale (P < 0.01) and duration of anterior disk displacement (P < 0.01). To elucidate the effects of EDPs on cultured human cells, human TMJ synovial cells were obtained from patients with unilateral TMJ ankylosis who underwent surgery for resection of the ankylotic segment. After treatment with different concentrations of EDPs in culture medium, genes and proteins expression were evaluated and analyzed. It was found that 25 and 50 μg/ml EDPs significantly increased gene expression and protein production of proinflammatory cytokines, IL-6, but not IL-1 and TNF-alpha. Sandwich enzyme immunoassays also revealed that EDPs levels significantly correlated with the IL-6 level (P < 0.01). These results in this study suggest that EDPs do induce inflammatory responses in human TMJ synovial cells and plays the key role in the development of TMD.  

References

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2.           Duca L, Floquet N, Alix AJ, Haye B, Debelle L. Elastin as a matrikine. Crit Rev Oncol Hematol. 2004;49(3):235-44.