Effects of cyclic equibiaxial mechanical stretch on α-BK and TRPV4 expression in equine chondrocytes

Hdud, Ismail M; Mobasheri, Ali; Loughna, Paul T.

doi:10.1186/2193-1801-3-59

Cited by 8 publications

(6 citation statements)

References 17 publications

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“…Cyclic biaxial stretch and chondrocyte passage and time in culture do not alter TRPV4 protein levels (Hdud et al, 2012, Hdud et al, 2014). Hypo-osmotic stimulation of isolated equine articular chondrocytes causes an increase in TRPV4 protein levels and ERK1/2 phosphorylation within 6 hours (Hdud et al, 2014). Treatment with PD98059, an ERK1/2 phosphorylation inhibitor, prevents the hypo-osmotic induced TRPV4 upregulation and suppresses TRPV4 expression under iso-osmotic conditions.…”

Section: Role Of Trpv4 In Cartilagementioning

confidence: 99%

“…Treatment with PD98059, an ERK1/2 phosphorylation inhibitor, prevents the hypo-osmotic induced TRPV4 upregulation and suppresses TRPV4 expression under iso-osmotic conditions. On the other hand, hyper-osmotic stimulation decreases TRPV4 protein expression at early time points (90 minutes and 3 hours) but returns to control levels by 6 hours (Hdud et al, 2014). These data suggest that during normal joint loading, which causes chondrocytes to experience large changes in the osmotic environment, TRPV4 expression levels may be altered in vivo .…”

Section: Role Of Trpv4 In Cartilagementioning

confidence: 99%

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TRPV4 as a therapeutic target for joint diseases

McNulty

Leddy

Liedtke

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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Biomechanical factors play a critical role in regulating the physiology as well as the pathology of multiple joint tissues, and have been implicated in the pathogenesis of osteoarthritis. Therefore, the mechanisms by which cells sense and respond to mechanical signals may provide novel targets for the development of disease-modifying osteoarthritis drugs (DMOADs). Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable cation channel that serves as a sensor of mechanical or osmotic signals in several musculoskeletal tissues, including cartilage, bone, and synovium. The importance of TRPV4 in joint homeostasis is apparent in patients harboring TRPV4 mutations, which result in the development of a spectrum of skeletal dysplasias and arthropathies. In addition, the genetic knockout of Trpv4 results in the development of osteoarthritis and decreased osteoclast function. In engineered cartilage replacements, chemical activation of TRPV4 can reproduce many of the anabolic effects of mechanical loading to accelerate tissue growth and regeneration. Overall, TRPV4 plays a key role in transducing mechanical, pain, and inflammatory signals within joint tissues, and thus is an attractive therapeutic target to modulate the effects of joint diseases. In pathological conditions in the joint, when the delicate balance of TRPV4 activity is altered, a variety of different tools could be utilized to directly or indirectly target TRPV4 activity.

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Section: Role Of Trpv4 In Cartilagementioning

confidence: 99%

Section: Role Of Trpv4 In Cartilagementioning

confidence: 99%

TRPV4 as a therapeutic target for joint diseases

McNulty

Leddy

Liedtke

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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“…This increase in intracellular Ca 2ϩ could be initiated by extracellular influx and augmented by release from intracellular stores (9,10). Recent studies suggest the transient receptor potential vanilloid (TRPV) 4 channel as a potential cellular osmosensor with possible involvement in mechanotransduction (17,27,54) and mediation of Ca 2ϩ influx to regulate volume recovery following hypo-osmotic stress in porcine articular chondrocytes (33). The TRPV4 channel is a Ca 2ϩ -permeable, nonselective cation channel (25,26).…”

mentioning

confidence: 99%

Effect of osmotic stress on the expression of TRPV4 and BK_Ca channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes

Hdud

Mobasheri

Loughna

2014

American Journal of Physiology-Cell Physiology

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Hdud IM, Mobasheri A, Loughna PT. Effect of osmotic stress on the expression of TRPV4 and BK Ca channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes. Am J Physiol Cell Physiol 306: C1050 -C1057, 2014. First published March 26, 2014 doi:10.1152/ajpcell.00287.2013.-The metabolic activity of articular chondrocytes is influenced by osmotic alterations that occur in articular cartilage secondary to mechanical load. The mechanisms that sense and transduce mechanical signals from cell swelling and initiate volume regulation are poorly understood. The purpose of this study was to investigate how the expression of two putative osmolyte channels [transient receptor potential vanilloid 4 (TRPV4) and largeconductance Ca 2ϩ -activated K ϩ (BKCa)] in chondrocytes is modulated in different osmotic conditions and to examine a potential role for MAPKs in this process. Isolated equine articular chondrocytes were subjected to anisosmotic conditions, and TRPV4 and BK Ca channel expression and ERK1/2 and p38 MAPK protein phosphorylation were investigated using Western blotting. Results indicate that the TRPV4 channel contributes to the early stages of hypo-osmotic stress, while the BK Ca channel is involved in responding to elevated intracellular Ca 2ϩ and mediating regulatory volume decrease. ERK1/2 is phosphorylated by hypo-osmotic stress (P Ͻ 0.001), and p38 MAPK is phosphorylated by hyperosmotic stress (P Ͻ 0.001). In addition, this study demonstrates the importance of endogenous ERK1/2 phosphorylation in TRPV4 channel expression, where blocking ERK1/2 by a specific inhibitor (PD98059) prevented increased levels of the TRPV4 channel in cells exposed to hypo-osmotic stress and decreased TRPV4 channel expression to below control levels in iso-osmotic conditions (P Ͻ 0.001).cartilage; chondrocyte; mitogen-activated protein kinase; osmotic; transient receptor potential vanilloid 4 ARTICULAR CARTILAGE covers the ends of bones in diarthrodial joints to provide protection from shearing and compressive forces generated secondary to joint articulation. Cartilage consists of extracellular matrix (ECM) and chondrocytes (3,30). ECM is composed mainly of collagen type II and proteoglycan (PG), as well as other small protein and glycoprotein components. Chondrocytes are the only resident cells found in articular cartilage. Their metabolic activity is strongly influenced by environmental factors, including soluble mediators, ECM composition, and dynamic changes induced by mechanical loading (13,46). Mechanical loading of articular cartilage induces fluid flow, mechanical membrane deformation, hydrostatic pressure, and osmotic stress (45).The osmolarity of the tissue fluid that bathes chondrocytes in the cartilage ECM is different from that of most other tissues and typically exceeds 380 mosM (47). The presence of polyanionic PG molecules in the ECM attracts cations, such as Na ϩ

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“…SK channels were activated after cyclic pressure-induced strain in human articular chondrocytes [ 147 ]. Cyclic stretching significantly increased the expression of BK channels in equine articular chondrocytes [ 148 ]. BK channels have a central role in the membrane-stretch-activated current in equine articular chondrocytes [ 48 ].…”

Section: Calcium-dependent Potassium Channelsmentioning

confidence: 99%

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

Takács

Kovács

Ebeid

et al. 2023

IJMS

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Musculoskeletal disorders represent one of the main causes of disability worldwide, and their prevalence is predicted to increase in the coming decades. Stem cell therapy may be a promising option for the treatment of some of the musculoskeletal diseases. Although significant progress has been made in musculoskeletal stem cell research, osteoarthritis, the most-common musculoskeletal disorder, still lacks curative treatment. To fine-tune stem-cell-based therapy, it is necessary to focus on the underlying biological mechanisms. Ion channels and the bioelectric signals they generate control the proliferation, differentiation, and migration of musculoskeletal progenitor cells. Calcium- and voltage-activated potassium (KCa) channels are key players in cell physiology in cells of the musculoskeletal system. This review article focused on the big conductance (BK) KCa channels. The regulatory function of BK channels requires interactions with diverse sets of proteins that have different functions in tissue-resident stem cells. In this narrative review article, we discuss the main ion channels of musculoskeletal stem cells, with a focus on calcium-dependent potassium channels, especially on the large conductance BK channel. We review their expression and function in progenitor cell proliferation, differentiation, and migration and highlight gaps in current knowledge on their involvement in musculoskeletal diseases.

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Effects of cyclic equibiaxial mechanical stretch on α-BK and TRPV4 expression in equine chondrocytes

Cited by 8 publications

References 17 publications

TRPV4 as a therapeutic target for joint diseases

TRPV4 as a therapeutic target for joint diseases

Effect of osmotic stress on the expression of TRPV4 and BK_Ca channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

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Effects of cyclic equibiaxial mechanical stretch on α-BK and TRPV4 expression in equine chondrocytes

Cited by 8 publications

References 17 publications

TRPV4 as a therapeutic target for joint diseases

TRPV4 as a therapeutic target for joint diseases

Effect of osmotic stress on the expression of TRPV4 and BKCa channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

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Effect of osmotic stress on the expression of TRPV4 and BK_Ca channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes