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Mapping cell diversity and position in temporomandibular joint osteoarthritis with pain at single cell resolution

ABSTRACT: Mapping cell diversity and position in temporomandibular joint osteoarthritis with pain at single cell resolution

PROVIDER: PRJNA1113678 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29090454_1.fastq.gz	Fastqsanger.gz
	SRR29090454_2.fastq.gz	Fastqsanger.gz
	SRR29090455_1.fastq.gz	Fastqsanger.gz
	SRR29090455_2.fastq.gz	Fastqsanger.gz

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Mapping cell diversity and position in temporomandibular joint osteoarthritis with pain at single cell resolution

Project description:Temporomandibular joint (TMJ) osteoarthritis (OA) is a highly prevalent disorder affecting patient’s quality of life due to joint pain and dysfunction. A comprehensive understanding of cell type diversity and their dynamics of TMJ along joint degeneration and pain is lacking. Here we established an inflammatory TMJOA mouse model via intra-articular injection of CFA (Complete Freund’s Adjuvant). TMJOA mice exhibited OA and orofacial pain, recapitulating hallmark symptoms in patients. We performed single-cell transcriptomic profiling of TMJ followed by the validation. We revealed cellular diversity, anatomic position, and cell dynamics of TMJ at single cell resolution along the joint degeneration and pain.

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Project description:Temporomandibular joint (TMJ) arthritis is a craniofacial disorder characterized by joint dysfunction and orofacial pain. Despite of its established roles in fluid and immune regulation, lymphatic regulation, and function in TMJ remain unknown. Using genetic report mouse, uDISCO tissue clearing, and 3D volume imaging, we defined lymphatic vessel morphology, structure, anatomic location in adult mouse TMJ. We demonstrate in a mouse model of TMJ osteoarthritis (TMJOA) that arthritis induces inflammatory lymphangiogenesis and leads to impaired synovial lymphatic functions, including decreases in synovial influx and lymph node fluid drainage. To establish the causative link between lymphatic remodeling and TMJOA, we performed lymphatic loss- and gain-of-function studies. Lymphatic deficiency exacerbated cartilage defects, bone loss, synovitis, synovial fibrosis, and pain behaviors in TMJOA mice. Conversely, lymphatic activation via a hydrogel-mediated VEGF-C delivery to TMJ reduced TMJ pain, inflammation, and arthritis-like pathogenesis. Therefore, we defined lymphatic structure in TMJ and found that lymphatic dysfunction drives TMJOA pathogenesis and pain, suggesting its potential as a therapeutic target.

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Project description:To investigate the functions of ncRNAs in temporomandibular joint osteoarthritis, we established temporomandibular joint osteoarthritis model induced by unilateral anterior crossbite. We then performed gene expression profiling analysis using data obtained from RNA-seq of condylar cartilage at 8 weeks of modeling.

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