Fluid shear-induced NFκB translocation in osteoblasts is mediated by intracellular calcium release

Chen, Neal X.; Geist, Derik J; Genetos, Damian C.; Pavalko, Fredrick M.; Duncan, Randall L.

doi:10.1016/s8756-3282(03)00159-5

Cited by 83 publications

(82 citation statements)

References 60 publications

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“…However this increase in Ca 2+ i in osteoblasts in response to mechanical loading has yet to be assigned a detailed function. We have shown this increase is required for release of ATP [28] and for the translocation of NF-κB in MC3T3-E1 cells in response to shear [36]. In this study, we found that chelation of Ca 2+ i with BAPTA completely abolished the FSS-induced pERK1/2, indicating that Ca 2+ i is critical for the phosphorylation of ERK1/2.…”

Section: Discussionsupporting

confidence: 51%

“…We have previously characterized a mechanosensitive, cation-selective channel (MSCC) and an L-type voltagesensitive Ca 2+ channel (L-VSCC) in osteoblasts [37] that, we postulate, act in concert to increase Ca 2+ entry in response to mechanical stimulation. We, and others, have shown these channels to be involved in increases in production and release of paracrine/autocrine factors [4,12,13,28] and changes in gene expression [36,38] in response to mechanical stimulation. We have recently shown that inhibition of the L-VSCC significantly attenuates bone formation associated with mechanical loading in rats and mice [17].…”

Section: Discussionmentioning

confidence: 91%

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Activation of extracellular-signal regulated kinase (ERK1/2) by fluid shear is Ca2+- and ATP-dependent in MC3T3-E1 osteoblasts

Liu

Genetos

Shao

et al. 2008

Bone

155

138

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To determine the role of Ca 2+ signaling in activation of the Mitogen-Activated Protein Kinase (MAPK) pathway, we subjected MC3T3-E1 pre-osteoblastic cells to inhibitors of Ca 2+ signaling during application of fluid shear stress (FSS). FSS only activated ERK1/2, rapidly inducing phosphorylation within 5 minutes of the onset of shear. Phosphorylation of ERK1/2 (pERK1/2) was significantly reduced when Ca 2+ i was chelated with BAPTA or when Ca 2+ was removed from the flow media. Inhibition of both the L-type voltage-sensitive Ca 2+ channel and the mechanosensitive cation-selective channel blocked FSS-induced pERK1/2. Inhibition of phospholipase C with U73122 significantly reduced pERK1/2. This inhibition did not result from block of intracellular Ca 2+ release, but a loss of PKC activation. Recent data suggests a role of ATP release and purinergic receptor activation in mechanotransduction. Apyrase-mediated hydrolysis of extracellular ATP completely blocked FSS-induced phosphorylation of ERK1/2, while addition of exogenous ATP to static cells mimicked the effects of FSS on pERK1/2. Two P2 receptors, P2Y 2 and P2X 7 , have been associated with the anabolic responses of bone to mechanical loading. Using both iRNA techniques and primary osteoblasts isolated from P2X 7 knockout mice, we found that the P2X 7 , but not the P2Y 2 , purinergic receptor was involved in ERK1/2 activation under FSS. These data suggest that FSS-induced ERK1/2 phosphorylation requires Ca 2+ -dependent ATP release, however both increased Ca 2+ i and PKC activation are needed for complete activation. Further, this ATP-dependent ERK1/2 phosphorylation is mediated through P2X 7 , but not P2Y 2 , purinergic receptors.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 91%

Activation of extracellular-signal regulated kinase (ERK1/2) by fluid shear is Ca2+- and ATP-dependent in MC3T3-E1 osteoblasts

Liu

Genetos

Shao

et al. 2008

Bone

155

138

View full text Add to dashboard Cite

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“…9). Interestingly, shear-induced, Ca 2ϩ -regulated NF B activation has been described in several other cell types, including neutrophils (51) and osteoblasts (52). Although NSCCs are not activated by BCR engagement in naive B cells, it is possible that costimulatory or coinhibitory receptors may differentially regulate the activity of NSCC and CRAC channels and thereby produce distinct physiological and immunological fates in them.…”

Section: Discussionmentioning

confidence: 99%

Distinct Calcium Channels Regulate Responses of Primary B Lymphocytes to B Cell Receptor Engagement and Mechanical Stimuli

Liu

Wen

et al. 2005

The Journal of Immunology

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Intracellular Ca2+ plays a central role in controlling lymphocyte function. Nonetheless, critical gaps remain in our understanding of the mechanisms that regulate its concentration. Although Ca2+-release-activated calcium (CRAC) channels are the primary Ca2+ entry pathways in T cells, additional pathways appear to be operative in B cells. Our efforts to delineate these pathways in primary murine B cells reveal that Ca2+-permeant nonselective cation channels (NSCCs) operate in a cooperative fashion with CRAC. Interestingly, these non-CRAC channels are selectively activated by mechanical stress, although the mechanism overlaps with BCR-activated pathways, suggesting that they may operate in concert to produce functionally diverse Ca2+ signals. NSCCs also regulate the membrane potential, which activates integrin-dependent binding of B cells to extracellular matrix elements involved in their trafficking and localization within secondary lymphoid organs. Thus, CRAC and distinct Ca2+ permeant NSCCs are differentially activated by the BCR and mechanical stimuli and regulate distinct aspects of B cell physiology.

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“…68,69 In vitro studies have shown that osteoblasts reorganize their cytoskeleton, upregulate transmembrane focal adhesion proteins, and express osteoblast-specific proteins involved in ECM adhesion such as osteopontin under fluid flow stimulation. [70][71][72] These known mechanisms of mechanical stimulate in bone cells and tissue have significant implications in synthetic bone scaffold design. Most importantly, to simulate the dynamic mechanical physiological environment, a synthetic scaffold must have similar mechanical properties (specifically elastic modulus) compared to native bone.…”

Section: Bone Mechanics and Mechanobiologymentioning

confidence: 99%

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Porter

Ruckh

Popat

2009

Biotechnology Progress

685

499

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Critical‐sized defects in bone, whether induced by primary tumor resection, trauma, or selective surgery have in many cases presented insurmountable challenges to the current gold standard treatment for bone repair. The primary purpose of a tissue‐engineered scaffold is to use engineering principles to incite and promote the natural healing process of bone which does not occur in critical‐sized defects. A synthetic bone scaffold must be biocompatible, biodegradable to allow native tissue integration, and mimic the multidimensional hierarchical structure of native bone. In addition to being physically and chemically biomimetic, an ideal scaffold is capable of eluting bioactive molecules (e.g., BMPs, TGF‐βs, etc., to accelerate extracellular matrix production and tissue integration) or drugs (e.g., antibiotics, cisplatin, etc., to prevent undesired biological response such as sepsis or cancer recurrence) in a temporally and spatially controlled manner. Various biomaterials including ceramics, metals, polymers, and composites have been investigated for their potential as bone scaffold materials. However, due to their tunable physiochemical properties, biocompatibility, and controllable biodegradability, polymers have emerged as the principal material in bone tissue engineering. This article briefly reviews the physiological and anatomical characteristics of native bone, describes key technologies in mimicking the physical and chemical environment of bone using synthetic materials, and provides an overview of local drug delivery as it pertains to bone tissue engineering is included. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009

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Fluid shear-induced NFκB translocation in osteoblasts is mediated by intracellular calcium release

Cited by 83 publications

References 60 publications

Activation of extracellular-signal regulated kinase (ERK1/2) by fluid shear is Ca2+- and ATP-dependent in MC3T3-E1 osteoblasts

Activation of extracellular-signal regulated kinase (ERK1/2) by fluid shear is Ca2+- and ATP-dependent in MC3T3-E1 osteoblasts

Distinct Calcium Channels Regulate Responses of Primary B Lymphocytes to B Cell Receptor Engagement and Mechanical Stimuli

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

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