Regulatory Genes Involved in TMJ Formation

Objectives: Temporomandibular joint disorders (TMJD) represent a significant health problem in the U.S. The significant heterogeneity in TMJD has not been well characterized and there are no known surrogate biomarkers to define TMJD subsets. The objective of the current study was to obtain a better understanding of TMJ biology by characterizing genes that are involved in TMJ development, which may serve as biomarkers for TMJD.

Methods: E16 mouse embryo sections were dissected by Laser Capture Microscopy. RNA samples obtained from captured articular surfaces of condyle and glenoid fossa were subjected to two rounds of amplification, followed by expression analysis using Affymetrix GeneChip mouse genome array 430 2.0, (>34,000 transcripts). All samples were analyzed in triplicate. Expression and location were characterized by in situ hybridization.

Results: 3,035 probe sets were enriched >2-fold in the condyle and 1,465 probe sets were enriched >2-fold in the fossa, compared to E16 whole mouse embryo reference samples. 220 condyle candidates represented signaling molecules and 190 represented transcription factors. Among genes enriched in the fossa, 170 represented signaling molecules and 95 represented transcription factors. In situ hybridization with E16.5 sections showed chondrogenesis-related genes Sox5, Sox6 and Sox9 to be expressed in highly distinctive patterns in the condyle. FGFR1,2 and 3, important in bone formation, were also present in the condyle in distinct expression patterns. Expression of Wnt 6 and Wnt receptor Fzd2, previously shown to play important roles in synovial joint formation,were also detected in the condyle articular region.

Conclusions: Differentially expressed genes present in the articular surfaces of the TMJ provide clues to the signaling and transcriptional pathways controlling TMJ development, and may provide novel biomarkers for the more accurate diagnosis of TMJD.

Supported by NIDCR awards K12 DE-14528 and K22DE-016309.