Bulk RNA‐seq analyses of mandibular condylar cartilage in a post‐traumatic TMJ osteoarthritis rabbit model

Abstract

ObjectiveThe temporomandibular joint (TMJ) is anatomically comprised of the mandibular condylar cartilage (CC) lined with fibrocartilaginous superficial zone and is crucial for eating and dental occlusion. TMJ osteoarthritis (OA) leads to pain, joint dysfunction and permanent loss of cartilage tissue. However, there are no drugs clinically available that ameliorate OA and little is known about global profiles of genes that contribute to TMJ OA. Furthermore, animal models that recapitulate the complexity of signalling pathways contributing to OA pathogenesis are crucial for designing novel biologics that thwart OA progression. We have previously developed a New Zealand white rabbit TMJ injury model that demonstrates CC degeneration. Here, we performed genome‐wide profiling to identify new signalling pathways critical for cellular functions during OA pathology.Materials and MethodsTemporomandibular joint OA was surgically induced in New Zealand white rabbits. Three months following injury, we performed global gene expression profiling of the TMJ condyle. RNA samples from TMJ condyles were subjected to sequencing. After raw RNA‐seq data were mapped to relevant genomes, differential expression was analysed with DESeq2. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted.Results/ConclusionsOur study revealed multiple pathways altered during TMJ OA induction including the Wnt, Notch and PI3K‐Akt signalling pathways. We demonstrate an animal model that recapitulates the complexity of the cues and signals underlying TMJ OA pathogenesis, which is essential for developing and testing novel pharmacologic agents to treat OA.

Connecting the dots towards precision orthodontics

“…Similarly, bulk RNA sequencing of the TMJ condyle in a rabbit model of osteoarthritis (OA) has identified Wnt, Notch and PI3K-Akt signalling pathways as key to the development of TMJ OA. 73 Transcriptome sequencing during orthodontic tooth movement (OTM) in mice have revealed differentially expressed genes that are involved in hypoxia, inflammatory and bone remodelling pathways. 74 Despite their nascent status, the future promise of omics discoveries to orthodontic therapies and risk assessment can be envisioned from the current examples of individualized biotherapeutics.…”

“…Transcriptomic studies on the developing mouse sutures have shown distinct RNA profiles and cellular signatures and localization 72 that provide a roadmap to future studies to identify customized therapies for craniosynostosis. Similarly, bulk RNA sequencing of the TMJ condyle in a rabbit model of osteoarthritis (OA) has identified Wnt, Notch and PI3K‐Akt signalling pathways as key to the development of TMJ OA 73 . Transcriptome sequencing during orthodontic tooth movement (OTM) in mice have revealed differentially expressed genes that are involved in hypoxia, inflammatory and bone remodelling pathways 74 .…”