Immunohistochemical Profiling in Temporomandibular Disorders: A Systematic Review of Biomarker Patterns in Synovial Tissue

ABSTRACT Background Temporomandibular disorders (TMD) are multifactorial conditions involving biomechanical dysfunction and progressive degeneration of the temporomandibular joint (TMJ) and surrounding tissues. Although affecting up to 36% of the population, their underlying molecular mechanisms remain incompletely understood. Immunohistochemical analysis of synovial biomarkers may help clarify processes involved in tissue degeneration and symptom development. Objective This systematic review investigates associations between immunohistochemical biomarkers in synovial tissue and morphological or symptomatic findings in TMD, with a focus on internal derangement and disc displacement. Methods A comprehensive literature search was conducted in MEDLINE/PubMed, EMBASE, Web of Science, and selected journals. Studies were screened according to PRISMA guidelines, and methodological quality was assessed using the Newcastle‐Ottawa Scale. Due to heterogeneity across studies, a narrative synthesis was performed. Results Thirteen studies involving 493 patients (mean age: 42.2 years; 82% women) were included, analyzing 23 different biomarkers. Frequently examined markers included MMPs, COX‐2, iNOS, interleukins, and VEGF. Several of these showed statistically significant correlations with histological, radiological, or clinical findings, suggesting roles in joint homeostasis, inflammation, and tissue remodeling associated with TMD. Conclusion Based on the reported associations with histological, radiological, and clinical findings, biomarkers were categorised into stage‐specific and functional groups, underscoring their relevance for disease stratification and prognosis. By revealing disease‐related patterns in progression and severity, synovial biomarkers have the potential to empower our understanding of the underlying mechanisms of TMD and contribute to more precise diagnostic and therapeutic approaches.