Regulation of chondrocyte biosynthetic activity by dynamic hydrostatic pressure: the role of TRP channels

Savadipour, Alireza; Nims, Robert J.; Katz, Dakota B; Guilak, Farshid

doi:10.1080/03008207.2020.1871475

Cited by 26 publications

(24 citation statements)

References 74 publications

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“…showed that umbilical cord MSC expanded in rotary cell culture system, which creates a combination of simultaneous HP, shear stress and buoyancy force, released approximately 3.8-fold more EVs compared to unstimulated group. [40] The underlying mechanism by which HP regulate stem cell dif- TGF-β production, [27] integrin proteins, [60] intermediate filament, [61] TRP ion channel family, [62] and intracellular calcium stores. [63] A recent review also pointed the possibility of HP affecting primary cilia or nuclei.…”

Section: Discussionmentioning

confidence: 99%

“…The underlying mechanism by which HP regulate stem cell differentiation has not yet been fully elucidated. Previous studies suggest this might happen through HP affecting the endogenous TGF‐β production, [ 27 ] integrin proteins, [ 60 ] intermediate filament, [ 61 ] TRP ion channel family, [ 62 ] and intracellular calcium stores. [ 63 ] A recent review also pointed the possibility of HP affecting primary cilia or nuclei.…”

Section: Discussionmentioning

confidence: 99%

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Hydrostatic pressure promotes chondrogenic differentiation and microvesicle release from human embryonic and bone marrow stem cells

Luo

Foster

Man

et al. 2022

Biotechnology Journal

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Mechanical stimulation plays in an important role in regulating stem cell differentiation and their release of extracellular vesicles (EVs). In this study, effects of low magnitude hydrostatic pressure (HP) on the chondrogenic differentiation and microvesicle release from human embryonic stem cells (hESCs) and human bone marrow stem cells (hBMSCs) are examined. hESCs were differentiated into chondroprogenitors and then embedded in fibrin gels and subjected to HP (270 kPa, 1 Hz, 5 days per week). hBMSC pellets were differentiated in chondrogenic media and subjected to the same regime. HP significantly enhanced ACAN expression in hESCs. It also led to a significant increase in DNA content, sGAG content and total sGAG/DNA level in hBMSCs. Furthermore, HP significantly increased microvesicle protein content released from both cell types. These results highlight the benefit of HP bioreactor in promoting chondrogenesis and EV production for cartilage tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hydrostatic pressure promotes chondrogenic differentiation and microvesicle release from human embryonic and bone marrow stem cells

Luo

Foster

Man

et al. 2022

Biotechnology Journal

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“…TRPV4 activation resulted in an increase in Col-II and sulfated glycosaminoglycans (GAGs) in cartilage. However, chondrocytes with GSK205 in the presence of a mechanical load expressed significantly lower levels of Col-II and higher levels of MMPs ( O'Conor et al, 2014 ; Trompeter et al, 2021a ; Savadipour et al, 2022 ). The effect of TRPV4 activation using GSK101 has been observed to be analogous to that of a mechanical load; chondrocytes treated with GSK101 decrease the synthesis of pro-inflammatory molecules and degradative enzymes ( Fu et al, 2021 ).…”

Section: Chondrocyte Mechanotransduction Mechanismsmentioning

confidence: 97%

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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“…TRPV4 is a polymodal Ca 2+ permeable non-selective ion channel (Liedtke, 2007), mutations in which leads to a phenotypically diverse range of severe skeletal conditions including lethal metatropic dysplasia, spondylometaphyseal dysoplasia (dwarfirm), and autosomal dominant brachyolmia (Camacho et al, 2010; Nilius & Voets, 2013; Nishimura et al, 2012). First discovered in 2000 (Liedtke et al, 2000; Strotmann et al, 2000), TRPV4 was initially found to be responsible for transducing osmotic signals (Liedtke & Friedman, 2003), but has since been implicated in the cell biosynthetic response to compressive loading (O’Conor et al, 2014), hydrostatic pressure (Savadipour et al, 2022) and oscillatory fluid shear (Corrigan et al, 2018). Previous work has found a critical role for TRPV4 in cartilage and bone cell function in vitro .…”

Section: Introductionmentioning

confidence: 99%

Mechanoregulatory role of TRPV4 in prenatal skeletal development

Khatib

Monsen

Ahmed

et al. 2022

Preprint

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Biophysical cues are essential for guiding skeletal development, but the mechanisms underlying the mechanical regulation of cartilage and bone formation are unknown. TRPV4 is a cell membrane ion channel responsible for transducing mechanical stimuli as a means of regulating skeletal cell homeostatic processes. Dysregulation of TRPV4 is associated with several skeletal developmental pathologies, indicating its involvement in cartilage and bone development, potentially in a mechanosensing capacity. In this study, we test the hypothesis that mechanically mediated prenatal skeletogenesis depends on TRPV4 activity. We first validate a novel model where we establish that dynamically loading embryonic mouse hindlimb explants cultured ex vivo promotes joint cartilage growth and morphogenesis, but not diaphyseal mineralization. We next reveal that TRPV4 protein expression is mechanically regulated and spatially localized to patterns of high biophysical stimuli in the femoral condyles of cultured limbs. Finally, we demonstrate that TRPV4 activity is crucial for the mechanical regulation of joint cartilage growth and shape, mediated via the control of cell proliferation and matrix biosynthesis, indicating a mechanism by which mechanical loading could direct morphogenesis during joint formation. We conclude that the regulatory pathways initiated by TRPV4 mechanotransduction are essential for the for the cartilage response to physical stimuli during skeletal development. Therefore, TRPV4 may be a valuable target for the development of therapeutic skeletal disease modifying drugs and developmentally-inspired tissue engineering strategies for skeletal repair.

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Regulation of chondrocyte biosynthetic activity by dynamic hydrostatic pressure: the role of TRP channels

Cited by 26 publications

References 74 publications

Hydrostatic pressure promotes chondrogenic differentiation and microvesicle release from human embryonic and bone marrow stem cells

Hydrostatic pressure promotes chondrogenic differentiation and microvesicle release from human embryonic and bone marrow stem cells

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

Mechanoregulatory role of TRPV4 in prenatal skeletal development

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