Sex-dimorphism of TMJOA
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE284256 | GEO | 2026/05/15
REPOSITORIES: GEO
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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.
2025-08-05 | GSE286871 | GEO
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:The discoidin domain receptor 1 (DDR-1) deficient mice exhibit a high incidence of osteoarthritis (OA) in the temporomandibular joint (TMJ) already at early age. Young DDR-1 knock-out mice show typical histological signs of OA, like, surface fissures, loss of proteoglycans, cluster formation of the chondrocytes, altered collagen types as well as atypical arrangement of the collagen fibrils. The isolated chondrocytes from the TMJ exhibit an osteoarthritic character with high amounts of Runt-related transcription factor 2 (runx-2) and collagen type I compared to low levels of SRY (sex determining region Y)-box 9 (sox-9) and aggrecan. Especially, the amount of discoidin domain receptor 2 (DDR2) is increased, which is key player of OA in this model. The gene expression as well as the proteins of the DDR-1-deficient chondrocytes from the TMJ could be influenced by a three dimensional matrix, combined with a knockdown of runx-2 or the stimulation with components of the extracellular matrix, for example nidogen-2. These manipulations caused the osteoarthritic chondrocytes of DDR-1-deficient mice to change their gene expression towards a signature of more physiological cartilage and will open new possibilities for future regenerative treatment options of temporomandibular disorders like OA of the TMJ.
2012-01-25 | GSE35297 | 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:Temporomandibular joint (TMJ) osteoarthritis (OA) affects a significant population, and there are no FDA-approved drugs for its treatment. Our previous studies showed that lysyl oxidase-like-2 (LOXL2) has anabolic effects on cartilage; however, whether LOXL2 plays a role in relieving TMJ-OA remains unknown. The goal of this study was to comprehensively investigate LOXL2 mechanism in TMJ protection, with an emphasis on transcriptomic network analysis, mitochondria, and apoptosis during TMJ-OA. We showed that the TMJ is transcriptionally unique compared to the knee, with elevated Loxl2 expression and cartilage-degenerative genes, potentially indicating its different mechanisms of action. Aggrecan promoter-specific homozygous deletion of Loxl2 in mice resulted in a cartilage-degeneration phenotype, mitochondrial dysfunction, NF-κβ-mediated chondrocyte apoptosis, and inflammatory immune response leading to TMJ-OA-like conditions. IL-1β is known to induce osteoarthritis via NF-κβ. With regard to translation, adenoviral-Loxl2 transduction in ex-vivo goat cartilage reduced the IL-1β-mediated degenerative effects. Importantly, LOXL2 preserved IL-1β–induced mitochondrial dysfunction, p62-mediated mitophagy, apoptosis, and extracellular matrix degeneration. Overall, we identified the protective role of LOXL2 during natural TMJ-OA-like progression and established LOXL2 as a potential candidate gene therapy candidate for future therapeutics.
2026-02-11 | GSE276978 | GEO
Project description:Temporomandibular joint (TMJ) osteoarthritis (OA) affects a significant population, and there are no FDA-approved drugs for its treatment. Our previous studies showed that lysyl oxidase-like-2 (LOXL2) has anabolic effects on cartilage; however, whether LOXL2 plays a role in relieving TMJ-OA remains unknown. The goal of this study was to comprehensively investigate LOXL2 mechanism in TMJ protection, with an emphasis on transcriptomic network analysis, mitochondria, and apoptosis during TMJ-OA. We showed that the TMJ is transcriptionally unique compared to the knee, with elevated Loxl2 expression and cartilage-degenerative genes, potentially indicating its different mechanisms of action. Aggrecan promoter-specific homozygous deletion of Loxl2 in mice resulted in a cartilage-degeneration phenotype, mitochondrial dysfunction, NF-κβ-mediated chondrocyte apoptosis, and inflammatory immune response leading to TMJ-OA-like conditions. IL-1β is known to induce osteoarthritis via NF-κβ. With regard to translation, adenoviral-Loxl2 transduction in ex-vivo goat cartilage reduced the IL-1β-mediated degenerative effects. Importantly, LOXL2 preserved IL-1β–induced mitochondrial dysfunction, p62-mediated mitophagy, apoptosis, and extracellular matrix degeneration. Overall, we identified the protective role of LOXL2 during natural TMJ-OA-like progression and established LOXL2 as a potential candidate gene therapy candidate for future therapeutics.
2026-02-11 | GSE277139 | 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
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.
2026-04-22 | GSE285766 | GEO
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:Changes in the mechanical homeostasis of the temporomandibular joint (TMJ) can lead to the initiation and progression of degenerative arthropathies such as osteoarthritis (OA). Cells sense and engage with their mechanical microenvironment through interactions with the extracellular matrix. In the mandibular condylar cartilage, the pericellular microenvironment is composed of type VI collagen. NG2/CSPG4 is a transmembrane proteoglycan that binds with type VI collagen, and has been implicated in the cell stress response through mechanical loading-sensitive signaling networks including ERK 1/2. The objective of this study is to define the role of NG2/CSPG4 in the initiation and progression of TMJ OA and to determine if NG2/CSPG4 engages ERK 1/2 in a mechanical loading dependent manner. In vivo, we induced TMJ OA in control and NG2/CSPG4 knockout mice using a surgical destabilization approach. In control mice, NG2/CSPG4 is depleted during the early stages of TMJ OA and NG2/CSPG4 knockout mice have more severe cartilage degeneration, elevated expression of key OA proteases, and suppression of OA matrix synthesis genes. In vitro, we characterized the transcriptome and protein from control and NG2/CSPG4 knockout cells and found significant dysregulation of the ERK 1/2 signaling axis. To characterize the mechanobiological response of NG2/CSPG4, we applied mechanical loads on cell-agarose-collagen scaffolds using a compression bioreactor and illustrate that NG2/CSPG4 knockout cells fail to mechanically activate ERK 1/2 and are associated with changes in the expression of the same key OA biomarkers measured in vivo. Together, these findings implicate NG2/CSPG4 in the mechanical homeostasis of TMJ cartilage and in the progression of degenerative arthropathies including OA.
2022-09-24 | GSE214077 | GEO