Preliminary evidence for conserved transcriptional response to adversity in adults with temporomandibular disorder.

UNLABELLED

Temporomandibular disorder (TMD) is one of the most common orofacial pain conditions. Alteration in immune functioning is one promising biological mechanism underlying pain in TMD. However, there is a gap in the understanding of molecular bases contributing to altered immune functioning in these patients.

OBJECTIVES

In the current study, we investigated whether individuals with TMD would exhibit differential activity of 3 specific transcription factors involved in inflammatory (nuclear factor-kappa B, NF-kB), antiviral (interferon-regulatory factors, IRF), and sympathetic (cAMP response element-binding protein, CREB) processes using a promoter-based bioinformatics analysis, which is characterized as the "Conserved Transcriptional Response to Adversity."

METHODS

Adults with TMD (n = 19) and without (n = 17) underwent a standardized clinical examination for TMD. A blood sample was collected for genome-wide transcriptional RNA profiling. Bioinformatic analyses tested for differential prevalence of proinflammatory and antiviral transcription factor activity in core promoter sequences from all genes showing >1.2-fold differential expression in TMD vs controls.

RESULTS

Promoter-based bioinformatic analyses of genome-wide transcriptome profiles confirmed upregulation of genes bearing response elements for proinflammatory transcription factor (NF-kB, = 0.002) and downregulation of genes with response elements for IRF ( = 0.037) in patients with TMD relative to controls. Results also indicated upregulated activity of CREB in patients with TMD ( = 0.08), consistent with increased activity of the sympathetic nervous system.

CONCLUSION

These results provide initial support that the regulation of immune pathways is altered in individuals with TMD. A shift of transcriptional resources to a proinflammatory state may be driven by psychosocial stress and contributes to symptoms associated with TMD.