Project description:Temporomandibular joint osteoarthritis (TMJ-OA), a subtype of temporomandibular joint dysfunction (TMD), is characterized by progressive cartilage degradation, subchondral bone erosion, and chronic pain. Although there has been extensive research on TMJ-OA, its etiology remains unknown. Age, hormonal factors, and excessive mechanical stress on the TMJ are proposed risk factors for TMJ-OA. Using microarrays, we discovered two disease susceptibility genes that have been suggested to be involved in the pathogenic mechanism of TMJ-OA.
Project description:Skeletal and synovial joint development involves distinct skeletal stem/progenitor populations. However, in neural crest-derived temporomandibular joint (TMJ), skeletal stem/progenitor lineage dynamics and ossification programs remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on mouse mandibular cartilage at embryonic day 16.5 (E16.5), postnatal day 0 (P0), and 13 weeks to construct a high-resolution atlas of skeletal stem/progenitor populations. The outer perichondrium lining the mandibular cartilage contained Lgr5⁺Pthlh⁺ cells expressing Dlx5, suggesting intramembranous ossification. In contrast, a previously uncharacterized Crabp1⁺ subpopulation within the inner perichondrium expressed Nrg1, Lsamp, Tac1, and Igfbp5, consistent with early cartilage progenitors biased toward endochondral ossification. These results reveal a spatial division of ossification modes with both intramembranous and endochondral growth and clarify the transcriptional regulation underlying TMJ development. Our findings provide a framework for understanding neural crest–derived skeletal stem/progenitor cell regulation and may inform cartilage regenerative strategies.
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.
Project description:We have performed single-cell RNA sequencing using 10x Genomics to study the cellular landscape of both healthy and osteoarhtritic temporomandibular joint (TMJ) condyle cartilage and disc tissues. Few studies have performed scRNA-seq on TMJ tissue, and those that have utilized mouse model or human embryo tissues. Here, we are the first to do so using a rat model and using an incisor splint OA-induced model. Understanding the cellular phenotypes within TMJ tissues and how these phenotypes respond to stress is a crucial step towards therepeutic advancements in the field.
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.
Project description:Pain is a predominant symptom of temporomandibular joint (TMJ) disorders, presenting significant clinical challenges due to their complexity and limited treatment options. This study investigated the therapeutic potential of butyrate, a gut microbiome metabolite, in a complete Freund’s adjuvant (CFA)-induced mouse model of TMJ inflammatory pain. Butyrate administration significantly alleviated TMJ pain and restored butyrate levels in mouse feces, plasma, and the spinal trigeminal nucleus caudalis (Sp5C). Additionally, it reversed TMJ pain-induced reductions in acetylation within Sp5C neurons, a critical epigenetic mechanism linked to pain states. Utilizing single-nucleus RNA sequencing (snRNA-seq) and single-nucleus ATAC sequencing (snATAC-seq), we profiled transcriptional and chromatin accessibility changes at the single-cell level.
Project description:Rheumatoid arthritis (RA) and other inflammatory arthritides are chronic joint diseases marked by inflammation and bone erosion, leading to progressive damage. While smaller joints are typically affected early, larger joints often become involved over time. Temporomandibular joint (TMJ) involvement occurs in over 50% of arthritis patients, causing severe jaw pain and functional impairment, yet it remains underrecognized and underresearched. Due to its unique mechanical and biological features, the TMJ may exhibit distinct pathomechanisms compared to other joints. To investigate these differences, we analyzed transcriptomic profiles of the TMJ, ankle joint, and alveolar bone in polyarthritic hTNF-α transgenic mice (hTNF-tg) and controls.
Project description:Background The temporomandibular joint (TMJ) is a complex joint consisting of the condyle, the temporal articu_x0002_lar surface, and the articular disc. Functions such as mastication, swallowing and articulation are accomplished by the movements of the TMJ. To date, the TMJ has been studied more extensively, but the types of TMJ cells, their differentiation, and their interrelationship during growth and development are still unclear and the study of the TMJ is limited. The aim of this study was to establish a molecular cellular atlas of the human embryonic temporomandibu_x0002_lar joint condyle (TMJC) by single-cell RNA sequencing, which will contribute to understanding and solving clinical problems. Results Human embryos at 3 and 4 months(3M,4M) of age are an important stage of TMJC development. We performed a comprehensive transcriptome analysis of TMJC tissue from human embryos at 3 and 4 months of age using single-cell RNA sequencing. A total of 16,624 cells were captured and the gene expression profiles of 15 cell clusters in human embryonic TMJC were determined, including 14 known cell types and one previously unknown cell type, "transition state cells (TSCs)". Immunofluorescence assays confirmed that TSCs are not the same cell cluster as mesen_x0002_chymal stem cells (MSCs). Pseudotime trajectory and RNA velocity analysis revealed that MSCs transformed into TSCs, which further differentiated into osteoblasts, hypertrophic chondrocytes and tenocytes. In addition, chondrocytes (CYTL1high+ THBS1high) from secondary cartilage were detected only in 4-month-old human embryonic TMJC. Conclusions Our study provides an atlas of differentiation stages of human embryonic TMJC tissue cells, which will contribute to an in-depth understanding of the pathophysiology of the TMJC tissue repair process and ultimately help to solve clinical problems.
Project description:Temporomandibular joint osteoarthritis (TMJ OA) is a prevalent degenerative disease characterized by chronic pain and impaired jaw function. Similarly to other OA affected limb joints, TMJ OA has shown increased prevalence across several demographic and biological factors. Sex has been considered a risk factor, with female patients reporting twice the incidence rate and suffering from greater symptom severity compared to male patients. However, due to a lack of relevant preclinical models, there is limited knowledge related to how sex differences impact TMJ OA pathophysiology.
Project description:The present study investigated the alterations of miRNA expression profiling in synovium of temporomandibular joint(TMJ) in a rat model of experimental unilateral mastication. The synovium tissue of TMJ condyles from rats with 4- and 8-weeks unilateral mastication were harvested to extract miRNA for profiling holistic expression alternations. A total of 20 differentially expressed miRNAs were identified. Except for 3 miRNAs with uncertain function, those miRNAs are associated with cell proliferation, invasion, and osteoblast differentiation process.