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: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: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.
Project description:Degenerative joint disease mainly manifests abnormal bone and cartilage remodeling, articular disc deformation and synovial inflammation, and it is closely related to intraarticular overload. Activation of the mechanosensitive channel transient receptor potential vanilloid 4 (TRPV4) can lead to degeneration of the temporomandibular joint (TMJ) disc. However, the potential mechanism by which TRPV4 leads to TMJ degeneration are still unclear. The results showed that TRPV4 activation promoted upregulation of chemokines including CXCL6 and CXCL13 in disc cells, and such chemokine release facilitated the proliferation and migration of FLSs and aggravated the TMJ degeneration in rat. Mechanistically, TRPV4-induced p38 MAPK signaling pathway activation promoted chemokine expression via the nuclear translocation of p38 and c-Fos, thereby promoting the proliferation and migration by CXCL-CXCR interaction.
Project description:We performed gene expression profiling analysis using data obtained from RNA-seq of condylar cartilage cells from post-traumatic temporomandibular joint osteoarthritis model to investigate the signaling pathways critical for cellular functions during temporomandibular joint osteoarthritis pathology.
Project description:We performed gene expression profiling analysis using data obtained from RNA-seq of 2 different cells from post-traumatic temporomandibular joint osteoarthritis model to investigate the signaling pathways critical for cellular functions during temporomandibular joint osteoarthritis pathology.
Project description:We conducted a genetic analysis of the developing temporo-mandibular joint (TMJ), a highly specialized synovial joint that permits movement and function of the mammalian jaw. First, we used laser capture microdissection to perform a genome-wide expression analysis of each of its developing components. The expression patterns of genes identified in this screen were examined in the TMJ and compared to other synovial joints including the shoulder joint and the hip joint. Striking differences were noted, indicating that the TMJ forms via a distinct molecular program. Several components of the Hedgehog (Hh) signaling pathway are among the genes identified in the screen, including Gli2, which is expressed specifically in the condyle and in the disk of the developing TMJ. We found that mice deficient in Gli2 display aberrant TMJ development such that the condyle loses its growth plate-like cellular organization and no disk is formed. In addition, we utilized a conditional strategy to remove activity of the Hh co-receptor encoded by Smo from chondrocyte progenitors. This cell autonomous loss of Hh signaling allows for disk formation, but the resulting structure fails to separate from the condyle. Thus, these experiments establish that Hh signaling acts at two distinct steps in disk morphogenesis, condyle initiation and disk-condyle separation, and provide a molecular framework for future studies of the TMJ. Experiment Overall Design: Mouse embryos fresh frozen and TMJ tissue captured by LCM. 3 samples in biological triplicate.
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.