Single cell analysis of healthy and diseased temporomandibular joint synovial fluid

Project Summary/Abstract Temporomandibular joint disorders (TMJDs) are a set of complex, poorly understood painful conditions that profoundly impact the quality of life of many children and adults in the US. Patients presenting with TMJDs often respond well to conservative therapy, but some patients endure multiple surgical procedures without relief. Indeed, the profound lack of mechanistic knowledge underpinning TMJDs has hindered the development of evidence-based therapy. As a result, there is a critical need to utilize the most recent technological advances in molecular biology towards developing novel therapeutic targets to improve care. In this project, we propose to utilize single cell RNA sequencing (sc-RNAseq) to identify and classify the cell populations and gene expression in TMJ synovial fluid. Our central hypothesis is that synovial fluid from symptomatic TMJD patients contains a unique cell population that is directly correlated to TMJ pain. In the UH2 phase of this project, we will develop the protocols for obtaining high quality TMJ synovial fluid and blood from healthy and symptomatic TMJD patients. In the UH3 phase of this project, we will perform single cell RNA sequencing and analysis on TMJ synovial fluid and blood from both healthy and symptomatic TMJD patients. We hypothesize that synovial fluid from symptomatic TMJD patients contains a unique cell population that can be identified by single cell RNA sequencing, is correlated with pain but not joint derangement, is present in blood from TMJD patients immediately preceding worsening symptoms, and is not present in healthy controls. The results from this study will provide mechanistic data at the single cell level regarding the initiation and resolution of TMJD.