Mural Cells Functions In Maintaining Matrix Homeostasis Within Temporomandibular Joint

To investigate the role of temporomandibular joint disc mural cells by comparing the changes in the extracellular matrix in normal state and ADD in human and mice. Raman spectroscopy, nanoindentation test, pentachrome staining and proteomics were used to test and compare human normal and ADD TMJ disc samples to investigate the change of ECM modification in TMJ tissue. An ADD mouse model was established to investigate ECM alterations. Single-cell transcriptome sequencing was applied to analyze change in transcriptome, and subpopulations of mural cells were analyzed to explore the roles of different states of mural cells. Transgenic mice were applied to trace disc mural cell and to observe their fate after ADD. Ultimately, single-cell data were analyzed to find the cell signaling pathways that regulate these processes. The results showed that the ECM of the posterior region of the human TMJ disc underwent fibrocartilage transformation in ADD, which was manifested as an increase of glycosaminoglycans; and the biomechanical modulus was significantly elevated after ADD which means that the posterior region showed functional alterations close to articular disc fibrocartilage. In contrast, a similar phenotype were found in mouse model . Lineage tracing revealed that mural cells could differentiate into a ECM transformation-associated fibroblast subpopulation. In the present study, we found that ECM changes of posterior disc region in the transcriptional properties and protein secretion in ADD contribute to their transformation into articular disc fibrocartilage. Mural cells participated in this process through the differentiation of specific functional fibroblasts.