Insulin-like growth factor-1 regulates the mechanosensitivity of chondrocytes by modulating TRPV4

Trompeter, Nicholas; Gardinier, Joseph D.; DeBarros, Victor M; Boggs, Mary; Gangadharan, Vimal; Cain, William J.; Hurd, Lauren; Duncan, Randall L.

doi:10.1016/j.ceca.2021.102467

Cited by 14 publications

(6 citation statements)

References 73 publications

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“…Transient receptor potential V anilin-like 4 (TRPV4) is a major member of the transient receptor potential (TRP) channel family 43 and can be activated by stress, heat, cell swelling, PH, and a variety of stimuli by pharmacological agonists 43 . TRPV4 is a non-selective positive ion channels that has been identi ed as being expressed in the kidney, brain, lung, heart, liver and testis, and has a key part to play in the control of a number of cellular functions.…”

Section: Discussionmentioning

confidence: 99%

Long Non-coding RNA MALAT1 Promotes Sepsis-Induced Testicular Injury by Targeting MiR-103-3p to Modulate TRPV4 Expression

Ning

Jiang

2022

Preprint

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Aberrant expression of long non-coding RNAs (lncRNAs) is closely related to the progression of sepsis. According to research, the lncRNA MALAT1 plays an important role in the multiple organ damage caused by sepsis. However, the mechanism associated with MALAT1 in septic testicular injury is not clear. We established an animal model of LPS-induced septic testicular injury and a cellular model of LPS-induced GC-1 cell injury in mice. H&E staining was performed to detect testicular injury after LPS treatment. MALAT1, inflammatory factors and related proteins expression levels in testicular tissues were determined using qRT-PCR, western blotting and immunohistochemistry. The ROS levels in tissue were detected by MDA and SOD. MALAT1, miR-103-3p and inflammatory factors expression levels in GC-1 were detected by qRT- PCR and ELISA assay. cell viability was determined by CCK-8. Western blot, immunofluorescence assay detected proteins expression. Correlation of MALAT1, miR-103-3p and TRPV4 was verified through dual luciferase reporter and Ago2-RIP. Within the present study, our findings suggest that MALAT1 expression is elevated in both cellular and animal models. Furthermore, we discovered that MALAT1 inhibits miR-103-3p expression at the post-transcriptional level while promoting TRPV4 expression, which promotes cellular inflammation and pyroptosis. As a result, we investigated the relationship between MALAT1, miR-103-3p, and TRPV4 and discovered that MALAT1 targets miR-103-3p, whereas miR-103-3p targets TRPV4. Our study showed that MALAT1 promotes testicular inflammation and pyroptosis through modulating miR-103-3p and TRPV4 in a septic testicular injury model, suggesting that MALAT1 may be a potential therapeutic target for septic testicular injury.

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Section: Discussionmentioning

confidence: 99%

Long Non-coding RNA MALAT1 Promotes Sepsis-Induced Testicular Injury by Targeting MiR-103-3p to Modulate TRPV4 Expression

Ning

Jiang

2022

Preprint

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“…Sox-9 exerts downstream effects through the AMP-response-binding protein (CREB)/p300 [34], and is also modulated by IKK-β/NF-kB, acting in parallel with HIF-2α and the BMP signaling system [38]. The Transient Receptor Potential Vanilloid 4 (TRPV4), an ion channel found by functional gene screening to play a pivotal role in chondrocyte mechanotransduction, stimulates Ca 2+ influx, Sox-9, and matrix synthesis [39,40]. TRPV4 is a regulatory checkpoint that also switches off also the IL-1 signaling through the downregulation of IL-1R [41].…”

Section: Sox-9 Nf-kb and Proinflammatory Cytokines Mediate Hypertroph...mentioning

confidence: 99%

Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis

Horváth,

Sólyom,

Székely

et al. 2023

IJMS

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Osteoarthritis (OA) is a complex disease of whole joints with progressive cartilage matrix degradation and chondrocyte transformation. The inflammatory features of OA are reflected in increased synovial levels of IL-1β, IL-6 and VEGF, higher levels of TLR-4 binding plasma proteins and increased expression of IL-15, IL-18, IL-10 and Cox2, in cartilage. Chondrocytes in OA undergo hypertrophic and senescent transition; in these states, the expression of Sox-9, Acan and Col2a1 is suppressed, whereas the expression of RunX2, HIF-2α and MMP-13 is significantly increased. NF-kB, which triggers many pro-inflammatory cytokines, works with BMP, Wnt and HIF-2α to link hypertrophy and inflammation. Altered carbohydrate metabolism and the upregulation of GLUT-1 contribute to the formation of end-glycation products that trigger inflammation via the RAGE pathway. In addition, a glycolytic shift, increased rates of oxidative phosphorylation and mitochondrial dysfunction generate reactive oxygen species with deleterious effects. An important surveyor mechanism, the YAP/TAZ signaling system, controls chondrocyte differentiation, inhibits ageing by protecting the nuclear envelope and suppressing NF-kB, MMP-13 and aggrecanases. The inflammatory microenvironment and synthesis of key matrix components are also controlled by SIRT1 and mTORc. Senescent chondrocytes represent the functional end stage of hypertrophic differentiation and characteristically upregulate p16 and p21, but also a variety of inflammatory cytokines, chemokines and metalloproteinases, developing the senescence-associated secretory phenotype. Senolysis with dendrobin, miR29b-5p and other agents has been shown to be efficient under experimental conditions, and appears to be a promising tool for the treatment of OA, as it restores COL2A1 and aggrecan synthesis, suppressing NF-kB and destructive metalloproteinases.

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“…Inflammation also affects the cytoskeleton, particularly filamentous actin (F-actin), as force transduction through F-actin is important in chondrocyte mechanotransduction ( Wang et al, 1993 ; Haudenschild et al, 2008 ; Trompeter et al, 2021b ; Dieterle et al, 2021 ). With exposure to IL-1α, F-actin of primary chondrocytes was reduced—an effect that was also seen in human OA cartilage samples.…”

Section: Chondrocyte Mechanotransduction Mechanismsmentioning

confidence: 99%

The Role of Mechanically-Activated Ion Channels Piezo1, Piezo2, and TRPV4 in Chondrocyte Mechanotransduction and Mechano-Therapeutics for Osteoarthritis

Gao

Hasan

Anderson

et al. 2022

Front. Cell Dev. Biol.

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Mechanical factors play critical roles in the pathogenesis of joint disorders like osteoarthritis (OA), a prevalent progressive degenerative joint disease that causes debilitating pain. Chondrocytes in the cartilage are responsible for extracellular matrix (ECM) turnover, and mechanical stimuli heavily influence cartilage maintenance, degeneration, and regeneration via mechanotransduction of chondrocytes. Thus, understanding the disease-associated mechanotransduction mechanisms can shed light on developing effective therapeutic strategies for OA through targeting mechanotransducers to halt progressive cartilage degeneration. Mechanosensitive Ca2+-permeating channels are robustly expressed in primary articular chondrocytes and trigger force-dependent cartilage remodeling and injury responses. This review discusses the current understanding of the roles of Piezo1, Piezo2, and TRPV4 mechanosensitive ion channels in cartilage health and disease with a highlight on the potential mechanotheraputic strategies to target these channels and prevent cartilage degeneration associated with OA.

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Insulin-like growth factor-1 regulates the mechanosensitivity of chondrocytes by modulating TRPV4

Cited by 14 publications

References 73 publications

Long Non-coding RNA MALAT1 Promotes Sepsis-Induced Testicular Injury by Targeting MiR-103-3p to Modulate TRPV4 Expression

Long Non-coding RNA MALAT1 Promotes Sepsis-Induced Testicular Injury by Targeting MiR-103-3p to Modulate TRPV4 Expression

Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis

The Role of Mechanically-Activated Ion Channels Piezo1, Piezo2, and TRPV4 in Chondrocyte Mechanotransduction and Mechano-Therapeutics for Osteoarthritis

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