The potential role of mechanosensitive ion channels in substrate stiffness-regulated Ca<sup>2+</sup>response in chondrocytes

Du, Genlai; Chen, Weiyi; Li, Li; Zhang, Quanyou

doi:10.1080/03008207.2021.2007902

Cited by 18 publications

(8 citation statements)

References 37 publications

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“…By culturing chondrocytes in polydimethylsiloxane (PDMS) substrates with different stiffness, Du et al discovered that intracellular Ca 2+ influx was dominated by TRPV4 at higher stiffness (78-197Kpa), while piezo type mechanosensitive ion channel component 1/2 (PIEZO1/2) mainly mediated lower stiffness (2–54 kpa) substrate-induced Ca 2+ response [ 106 ]. The selective activations of mechanosensors in response to variant microenvironment stiffness might explain the differences in metabolism of chondrocytes from normal or OA cartilage, which have distinct matrix stiffness.…”

Section: Matrix Stiffness As a Promising Microenvironmental Factor In...mentioning

confidence: 99%

Alteration in cartilage matrix stiffness as an indicator and modulator of osteoarthritis

Song,

Zeng,

et al. 2024

Bioscience Reports

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Osteoarthritis (OA) is characterized by cartilage degeneration and destruction, leading to joint ankylosis and disability. The major challenge in diagnosing OA at early stage is not only lack of clinical symptoms but also the insufficient histological and immunohistochemical signs. Alteration in cartilage stiffness during OA progression, especially at OA initiation, has been confirmed by growing evidences. Moreover, the stiffness of cartilage extracellular matrix (ECM), pericellular matrix (PCM) and chondrocytes during OA development are dynamically changed in unique and distinct fashions, revealing possibly inconsistent conclusions when detecting cartilage matrix stiffness at different locations and scales. In addition, it will be discussed regarding the mechanisms through which OA-related cartilage degenerations exhibit stiffened or softened matrix, highlighting some critical events that generally incurred to cartilage stiffness alteration, as well as some typical molecules that participated in constituting the mechanical properties of cartilage. Finally, in vitro culturing chondrocytes in various stiffness-tunable scaffolds provided a reliable method to explore the matrix stiffness-dependent modulation of chondrocyte metabolism, which offers valuable information on optimizing implant scaffolds to maximally promote cartilage repair and regeneration during OA. Overall, this review systematically and comprehensively elucidated the current progresses in the relationship between cartilage stiffness alteration and OA progression. We hope that deeper attention and understanding in this researching field will not only develop more innovative methods in OA early detection and diagnose, but also provide promising ideas in OA therapy and prognosis.

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Section: Matrix Stiffness As a Promising Microenvironmental Factor In...mentioning

confidence: 99%

Alteration in cartilage matrix stiffness as an indicator and modulator of osteoarthritis

Song,

Zeng,

et al. 2024

Bioscience Reports

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“…Many studies have reported that Piezo1 acts as the upstream of TRPV4 by binding through phospholipase and triggers a consistent Ca 2+ influx, leading to a variety of effects including adhesion junctions disruption and monocyte adhesion in endothelial cell [ 85 ], attenuated proliferation in osteoblastic cell [ 173 ], cell necrosis in pancreatic acinar cell [ 172 ]. One possible explanation for the functional interaction is that the two channels in the same cell are responsible for different degrees and ranges of mechanical stimuli: Piezo1 transduces transient and mild mechanical signals, while TRPV4 transduces sustained and severe mechanical signals [ 174 , 175 ]. However, we don’t mean that Piezo1 interacts with another Piezo1 in the same cell.…”

Section: Piezo1 Affects the Biological Function Of The Digestive Systemmentioning

confidence: 99%

Piezo1 in Digestive System Function and Dysfunction

He,

Xie,

Xiao

et al. 2023

IJMS

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Piezo1, a non-selective cation channel directly activated by mechanical forces, is widely expressed in the digestive system and participates in biological functions physiologically and pathologically. In this review, we summarized the latest insights on Piezo1’s cellular effect across the entire digestive system, and discussed the role of Piezo1 in various aspects including ingestion and digestion, material metabolism, enteric nervous system, intestinal barrier, and inflammatory response within digestive system. The goal of this comprehensive review is to provide a solid foundation for future research about Piezo1 in digestive system physiologically and pathologically.

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“…On the other hand, TRPV4, Piezo1, and Piezo2 channels play a role in Ca 2+ signaling dependent on substrate stiffness. Specifically, TRPV4 responds to stiffer substrates, while Piezo1/2 to less stiff substrates, making these ion channels potential targets for OA treatment ( Du et al, 2021 ).…”

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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The potential role of mechanosensitive ion channels in substrate stiffness-regulated Ca²⁺response in chondrocytes

Cited by 18 publications

References 37 publications

Alteration in cartilage matrix stiffness as an indicator and modulator of osteoarthritis

Alteration in cartilage matrix stiffness as an indicator and modulator of osteoarthritis

Piezo1 in Digestive System Function and Dysfunction

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

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The potential role of mechanosensitive ion channels in substrate stiffness-regulated Ca2+response in chondrocytes

Cited by 18 publications

References 37 publications

Alteration in cartilage matrix stiffness as an indicator and modulator of osteoarthritis

Alteration in cartilage matrix stiffness as an indicator and modulator of osteoarthritis

Piezo1 in Digestive System Function and Dysfunction

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

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The potential role of mechanosensitive ion channels in substrate stiffness-regulated Ca²⁺response in chondrocytes