Single-cell transcriptomic and spatial subcellular landscape of the articular disk synovium in mouse temporomandibular joint osteoarthritis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE276131 | GEO | 2025/12/31
REPOSITORIES: GEO
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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.
2020-09-18 | GSE158106 | GEO
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.
2025-04-02 | GSE267942 | GEO
Project description:Background Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA. Materials and Methods To determine whether Dspp+/- mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp+/-, and Dspp homozygous (Dspp-/-) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp+/- mice over time, condyles of Dspp+/- and WT mice were analyzed radiologically, histologically, and immunohistochemically. Results Micro-CT and histomorphometric analyses revealed that Dspp+/- and Dspp-/- mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp-/- mice which exhibited tooth loss, Dspp+/- mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp+/- mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp+/- mice showed increased distribution of osteoclast in the subchondal bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage. Conclusions Dspp+/- mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.
2024-03-19 | GSE261528 | GEO
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.
2025-06-25 | GSE295404 | GEO
Project description:Single-cell transcriptomic and spatial subcellular landscape of the articular disk synovium in mouse temporomandibular joint osteoarthritis
| PRJNA1154967 | ENA
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.
2009-10-23 | E-GEOD-17473 | biostudies-arrayexpress
Project description:<p><strong>INTRODUCTION:</strong> Temporomandibular joint (TMJ) osteoarthritis (OA) is a common TMJ degenerative disease with an unclear mechanism. Synovial fluid (SF), an important component of TMJ, contains various proteins and metabolites that may directly contribute to OA. The present study aimed to investigate the influence of SF in TMJOA at the metabolite level.</p><p><strong>METHODS:</strong> Untargeted and widely targeted metabolic profiling were employed to identify metabolic changes in SF of 90 patients with different TMJOA grades according to TMJ magnetic resonance imaging.</p><p><strong>RESULTS:</strong> A total 1498 metabolites were detected. Most of the metabolites were amino acids and associated metabolites, benzene and substituted derivatives, and lipids. Among patients with mild, moderate and severe TMJOA, 164 gradually increasing and 176 gradually decreasing metabolites were identified, indicating that biosynthesis of cofactors, choline metabolism, mineral absorption and selenocompound metabolism are closely related to TMJOA grade. Combined metabolomics and clinical examination revealed 37 upregulated metabolites and 16 downregulated metabolites in patients with pain, of which 19 and 26 metabolites were positively and negatively correlated, respectively, with maximum interincisal opening. A model was constructed to diagnose TMJOA grade and nine biomarkers were identified. The identified metabolites are key to exploring the mechanism of TMJOA.</p><p><strong>DISCUSSION:</strong> In the present study, a metabolic profile was constructed and assessed using a much larger number of human SF samples from patients with TMJOA, and a model was established to contribute to the diagnosis of TMJOA grade. The findings expand our knowledge of metabolites in human SF of TMJOA patients, and provide an important basis for further research on the pathogenesis and treatment of TMJOA.</p>
2025-05-27 | MTBLS9665 | MetaboLights
Project description:<p><strong>INTRODUCTION:</strong> Temporomandibular joint (TMJ) osteoarthritis (OA) is a common TMJ degenerative disease with an unclear mechanism. Synovial fluid (SF), an important component of TMJ, contains various proteins and metabolites that may directly contribute to OA. The present study aimed to investigate the influence of SF in TMJOA at the metabolite level.</p><p><strong>METHODS:</strong> Untargeted and widely targeted metabolic profiling were employed to identify metabolic changes in SF of 90 patients with different TMJOA grades according to TMJ magnetic resonance imaging.</p><p><strong>RESULTS:</strong> A total 1498 metabolites were detected. Most of the metabolites were amino acids and associated metabolites, benzene and substituted derivatives, and lipids. Among patients with mild, moderate and severe TMJOA, 164 gradually increasing and 176 gradually decreasing metabolites were identified, indicating that biosynthesis of cofactors, choline metabolism, mineral absorption and selenocompound metabolism are closely related to TMJOA grade. Combined metabolomics and clinical examination revealed 37 upregulated metabolites and 16 downregulated metabolites in patients with pain, of which 19 and 26 metabolites were positively and negatively correlated, respectively, with maximum interincisal opening. A model was constructed to diagnose TMJOA grade and nine biomarkers were identified. The identified metabolites are key to exploring the mechanism of TMJOA.</p><p><strong>DISCUSSION:</strong> In the present study, a metabolic profile was constructed and assessed using a much larger number of human SF samples from patients with TMJOA, and a model was established to contribute to the diagnosis of TMJOA grade. The findings expand our knowledge of metabolites in human SF of TMJOA patients, and provide an important basis for further research on the pathogenesis and treatment of TMJOA.</p>
2025-05-27 | MTBLS9662 | MetaboLights
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.
2018-05-16 | GSE114499 | GEO
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.
2025-07-01 | GSE298882 | GEO