Mechanical overload induces <scp>TMJ</scp> disc degeneration via <scp>TRPV4</scp> activation

Cui, Shengjie; Yang, Fujia; Wang, Xuedong; Mao, Zebin; Gu, Yan

doi:10.1111/odi.14595

Cited by 3 publications

(3 citation statements)

References 48 publications

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“…Under moderate mechanical stress, activation of TRPV4 has been confirmed to mediate anabolic responses ( O’Conor et al, 2014 ). However, under excessive mechanical stress, high TRPV4 expression and enhanced Ca 2+ influx can induce chondrocyte apoptosis ( Xu et al, 2019 ) and promote degenerative changes in the TMJ disc ( Cui et al, 2023 ). Piezo1 and Piezo2 are also Ca 2+ -permeable channels in chondrocytes that are activated under abnormal strain ( Du G. et al, 2020 ).…”

Section: Elements In Mechanotransductionmentioning

confidence: 99%

“…Dynamic tensile strain can downregulate the catabolic activity of fibrocartilage cells in an inflammatory environment by inhibiting expression of a variety of MMPs (including MMP-3, -7, -8, -9, -13, −16, −17, and −19) ( Deschner et al, 2006 ). However, overload of mechanical force can induce upregulation of inflammatory cytokines and multiple subtypes of MMPs in TMJ disc cells, which is associated with TRPV4 activation and Ca 2+ influx ( Cui et al, 2023 ). Furthermore, aquaporin-1 (AQP-1) has been reported to mediate the effects of stress on TMJ disc cells ( Loreto et al, 2012 ).…”

Section: Effects Of Mechanical Loading On the Synovial Membrane And Discmentioning

confidence: 99%

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Critical signaling molecules in the temporomandibular joint osteoarthritis under different magnitudes of mechanical stimulation

Liu,

Jia,

et al. 2024

Front. Pharmacol.

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The mechanical stress environment in the temporomandibular joint (TMJ) is constantly changing due to daily mandibular movements. Therefore, TMJ tissues, such as condylar cartilage, the synovial membrane and discs, are influenced by different magnitudes of mechanical stimulation. Moderate mechanical stimulation is beneficial for maintaining homeostasis, whereas abnormal mechanical stimulation leads to degeneration and ultimately contributes to the development of temporomandibular joint osteoarthritis (TMJOA), which involves changes in critical signaling molecules. Under abnormal mechanical stimulation, compensatory molecules may prevent degenerative changes while decompensatory molecules aggravate. In this review, we summarize the critical signaling molecules that are stimulated by moderate or abnormal mechanical loading in TMJ tissues, mainly in condylar cartilage. Furthermore, we classify abnormal mechanical stimulation-induced molecules into compensatory or decompensatory molecules. Our aim is to understand the pathophysiological mechanism of TMJ dysfunction more deeply in the ever-changing mechanical environment, and then provide new ideas for discovering effective diagnostic and therapeutic targets in TMJOA.

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Section: Elements In Mechanotransductionmentioning

confidence: 99%

Section: Effects Of Mechanical Loading On the Synovial Membrane And Discmentioning

confidence: 99%

Critical signaling molecules in the temporomandibular joint osteoarthritis under different magnitudes of mechanical stimulation

Liu,

Jia,

et al. 2024

Front. Pharmacol.

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“…While the etiology remains largely unknown, there are some reported contributing factors. Mechanical overload of the TMJ [ 16 ], a perforation of the TMJ disc [ 17 ], or a disc displacement in the TMJ [ 18 – 20 ] have been reported as potential contributing factors. Further, systemic arthritis stems from underlying systemic diseases such as rheumatoid arthritis, juvenile arthritis, and psoriatic arthritis, representing a localized manifestation of a broader systemic inflammatory process.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Treatments of Temporomandibular Disorders: A Systematic Review Including a Network Meta-Analysis

Christidis,

Al-Moraissi,

Barjandi

et al. 2023

Drugs

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Objective Temporomandibular disorders (TMD) comprise a cluster of conditions with a wide range of etiological factors that causes pain and discomfort in the masticatory muscles (TMD-M) and temporomandibular joints (TMD-J). More than 50% of the patients with TMD report regular usage of drugs. However, there is still no consensus, nor is there any evidence-based support for clinicians when choosing between different drugs. Therefore, this systematic review, including a network meta-analysis (NMA), aimed to evaluate the scientific evidence and discuss the pharmacological treatment options available to treat painful TMD. Method An electronic search was undertaken to identify randomized controlled trials (RCTs) investigating pharmacological treatments for TMD-M and/or TMD-J, published until 6 April 2023. Since only 11 articles could be used for an NMA regarding TMD-M, a narrative synthesis was also performed for all 40 included RCTs. The quality of evidence was rated according to Cochrane’s tool for assessing risk of bias, while the certainty of evidence was rated according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results When it comes to TMD-M, evidence arises for wet needling therapies with BTX-A, granisetron, and PRP as well as muscle relaxants. For TMD-J, evidence points toward pharmacological treatment approaches including non-steroidal antiinflammatory drugs (NSAIDs) and glucocorticosteriods (for inflammatory conditions) as well as hyaluronic acid and dextrose. Conclusions The evidence clearly indicates that the pharmacological treatment approaches differ between TMD-M and TMD-J. Therefore, it is of great importance to first try to uncover each patient’s individual and multifactorial etiology and then employ a multifaceted treatment strategy, including pharmacological treatment approaches. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-023-01971-9.

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Modulating TRPV4 Channel Activity in Pro-Inflammatory Macrophages within the 3D Tissue Analog

Babaniamansour,

Jacho,

Niedzielski

et al. 2024

Biomedicines

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Investigating macrophage plasticity emerges as a promising strategy for promoting tissue regeneration and can be exploited by regulating the transient receptor potential vanilloid 4 (TRPV4) channel. The TRPV4 channel responds to various stimuli including mechanical, chemical, and selective pharmacological compounds. It is well documented that treating cells such as epithelial cells and fibroblasts with a TRPV4 agonist enhances the Ca2+ influx to the cells, which leads to secretion of pro-inflammatory cytokines, while a TRPV4 antagonist reduces both Ca2+ influx and pro-inflammatory cytokine secretion. In this work, we investigated the effect of selective TRPV4 modulator compounds on U937-differentiated macrophages encapsulated within three-dimensional (3D) matrices. Despite offering a more physiologically relevant model than 2D cultures, pharmacological treatment of macrophages within 3D collagen matrices is largely overlooked in the literature. In this study, pro-inflammatory macrophages were treated with an agonist, 500 nM of GSK1016790A (TRPV4(+)), and an antagonist, 10 mM of RN-1734 (TRPV4(−)), to elucidate the modulation of the TRPV4 channel at both cellular and extracellular levels. To evaluate macrophage phenotypic alterations within 3D collagen matrices following TRPV4 modulator treatment, we employed structural techniques (SEM, Masson’s trichrome, and collagen hybridizing peptide (CHP) staining), quantitative morphological measures for phenotypic assessment, and genotypic methods such as quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Our data reveal that pharmacological modulation of the macrophage TRPV4 channel alters the cytoskeletal structure of macrophages and influences the 3D structure encapsulating them. Moreover, we proved that treating macrophages with a TRPV4 agonist and antagonist enhances the expression of pro- and anti-inflammatory genes, respectively, leading to the upregulation of surface markers CD80 and CD206. In the TRPV4(−) group, the CD206 gene and CD206 surface marker were significantly upregulated by 9- and 2.5-fold, respectively, compared to the control group. These findings demonstrate that TRPV4 modulation can be utilized to shift macrophage phenotype within the 3D matrix toward a desired state. This is an innovative approach to addressing inflammation in musculoskeletal tissues.

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Mechanical overload induces TMJ disc degeneration via TRPV4 activation

Cited by 3 publications

References 48 publications

Critical signaling molecules in the temporomandibular joint osteoarthritis under different magnitudes of mechanical stimulation

Critical signaling molecules in the temporomandibular joint osteoarthritis under different magnitudes of mechanical stimulation

Pharmacological Treatments of Temporomandibular Disorders: A Systematic Review Including a Network Meta-Analysis

Modulating TRPV4 Channel Activity in Pro-Inflammatory Macrophages within the 3D Tissue Analog

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