Lymphatic dysfunction drives inflammatory temporomandibular joint osteoarthritis (TMJOA) and pain
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ABSTRACT:
PROVIDER: PRJNA1254606 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
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| SRR33291371_1.fastq.gz | Fastqsanger.gz | |||
| SRR33291371_2.fastq.gz | Fastqsanger.gz |
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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.
2025-06-25 | GSE295404 | 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:To investigate differentially expressed miRNAs in synovium of human temporomandibular joint osteoarthritis (TMJOA), we performed miRNA high-throughput sequencing in synovium of human TMJOA.
2022-06-10 | GSE205684 | GEO
Project description:Background: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease marked by the progressive degeneration of cartilage and underlying bone, resulting in pain and functional impairment. Despite current conservative treatments such as physical therapy and NSAIDs, the etiology and pathophysiology of TMJOA are unclear, making effective management difficult. Finding reliable biomarkers for early identification and new therapeutic targets is crucial to improve treatment outcomes.
2025-03-06 | GSE289871 | GEO
Project description:To investigate differentially expressed lncRNAs,circRNAs,miRNAs and mRNAs in synovium of human temporomandibular joint osteoarthritis (TMJOA), we performed RNA high-throughput sequencing in synovium of human TMJOA. We then performed gene expression profiling analysis using data obtained from RNA-seq .
2022-06-07 | GSE205389 | GEO
Project description:This project investigates the role of RalA in temporomandibular joint osteoarthritis using a mouse MIA-induced TMJOA model and primary mouse temporomandibular joint condylar chondrocytes. Transcriptomic profiling of siNC- and siRalA-transfected chondrocytes was performed to identify RalA-regulated inflammatory and extracellular matrix remodeling pathways. The study identifies CCN3 as a RalA-regulated secreted mediator that amplifies inflammatory cytokine production and cartilage catabolism.
2026-07-31 | GSE338438 | GEO
Project description:Background and objectives: Current clinical interventions lack effective strategies to arrest temporomandibular joint osteoarthritis (TMJOA) progression. Emerging evidence highlights the therapeutic potential of microRNAs (miRNAs) in osteoarthritis (OA) management, though critical challenges persist regarding delivery efficiency, including unsatisfactory cellular uptake, immunogenicity, and structural instability of miRNA-based therapeutics. Methods and results: Considering the powerful editability of tetrahedral framework nucleic acids (tFNAs) for gene delivery, we engineered a novel nanoscale gene delivery system using tetrahedral framework nucleic acids functionalized with miR-143-3p (tFNAs-143). Through comprehensive in vivo modeling of TMJOA destabilization and in vitro simulation of IL-1β-induced inflammatory microenvironments, we systematically investigated the therapeutic efficacy and molecular mechanisms underlying OA pathophysiology of tFNAs-143. Our results demonstrated that tFNAs-143 exhibited excellent cellular internalization in chondrocytes and effectively mitigated TMJOA progression by impeding ferritinophagy-mediated ferroptosis. Conclusions: This study advanced miRNA delivery technology for TMJOA therapy, deepened the insights into TMJOA pathogenesis, and proposed a promising nano therapeutic strategy for developing targeted TMJOA therapies.
2026-01-21 | GSE303194 | GEO
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:<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:Background: Temporomandibular joint (TMJ) degenerative diseases are increasingly affecting elderly populations, with aging being a significant risk factor driving the TMJ changes. This study aims to explore the shared characteristics between aging and TMJ degenerative diseases at the tissue level, and to identify aging-related signature genes in TMJ degenerations using bioinformatics approaches. Methods: Young (2 months of age, n=7) and aged (18 months of age, n=6) mice’s condyles were used to construct an aging dataset. Overlapping genes were selected from differentially expressed genes in the TMJOA dataset, aging dataset and mechanical stimulation dataset. Temporomandibular joint osteoarthritis-associated and aging-related differentially expressed genes (TMJOA-ARDEGs) were identified through Weighted gene co-expression network analysis. Functional enrichment analysis and Protein-Protein Interaction networks were employed. Machine learning was applied to select Hub temporomandibular joint osteoarthritis-associated and aging-related differentially expressed genes (Hub TMJOA-ARDEGs). An age-related TMJOA mouse model (18 months of age) was established and grouped based on the micro-CT and the modified Mankin scores. The expression changes of key Hub TMJOA-ARDEGs were verified by immunohistochemical staining. The Mann-Whitney U test was used in non-normally distributed data, presented as [median (interquartile range)]. Results: Fifty-two TMJOA-ARDEGs were identified, with functional enrichment analysis revealed that these genes participate in circadian rhythm and apoptosis. Eight Hub TMJOA-ARDEGs were identified, ANK1, MELTF, FERMT3, MDFI, CXCL14, EPHA3, SMOC2 and NR1D1. Based on the micro-CT, 12 TMJs of aged mice were divided into the TMJOA group (n=6) and the healthy group (n=6). Micro-CT revealed bone resorption in the TMJOA group compared to the healthy group, with a decrease in BV/TV (p<0.05) and an increase in Tb.Sp (p<0.05). The modified Mankin scores showed that the TMJOA group had a score of 5.61 (2.28), higher than the healthy group's score of 0.83 (1.28), p<0.01. These results confirm the validity of the model grouping. Among the Hub TMJOA-ARDEGs, NR1D1 is a key gene involved in regulating circadian rhythm. In immunohistochemical staining, the expression level of NR1D1 showed significantly elevated expression in osteoarthritis mice (p<0.01). Conclusion: NR1D1, a negative feedback regulator in the circadian rhythm loop, is a characteristic gene associated with both aging and TMJ degenerative diseases.
2026-04-26 | GSE315467 | GEO