What is the role of the convective current density in the real-time calcium response of cultured bone cells to fluid flow?

Hung, Clark T.; Allen, Fred; Pollack, Solomon R.; Brighton, Carl T.

doi:10.1016/0021-9290(96)84535-0

Cited by 72 publications

(30 citation statements)

References 21 publications

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“…In a parallel plate flow chamber, an increase in chemotransport is predicted only between 0 and 0.25 dyn/cm 2 (3). Dose-dependent shear stress, release of NO, and shear-induced increases of intracellular calcium have been demonstrated to be independent of chemotransport (14,22,34). Therefore, it is unlikely that chemotransport mediates flow-induced signaling at shear above 0.25 dyn/ cm 2 .…”

Section: Discussionmentioning

confidence: 99%

Temporal gradients in shear stimulate osteoblastic proliferation via ERK1/2 and retinoblastoma protein

Jiang

White

Stevens

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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The effects of pulsatile flow (temporal gradients in fluid shear) on rat UMR106 cells and rat primary osteoblastic cells were studied. Pulsatile flow induced a 95% increase in S-phase UMR106 cells compared with static controls. In contrast, ramped steady flow stimulated only a 3% increase. Similar patterns of S-phase induction were also observed in rat primary osteoblastic cells. Pulsatile flow significantly increased relative UMR106 cell number by 37 and 62% at 1.5 and 24 h, respectively. Pulsatile flow also significantly increased extracellular signal-regulated kinase (ERK1/2) phosphorylation by 418%, whereas ramped steady flow reduced ERK1/2 activation to 17% of control. Correspondingly, retinoblastoma protein was significantly phosphorylated by pulsatile fluid flow. Inhibition of mitogen-activated protein (MAP)/ERK kinase (MEK)1/2 by U0126 (a specific MEK1/2 inhibitor) reduced shear-induced ERK1/2 phosphorylation and cell proliferation. These findings suggest that temporal gradients in fluid shear stress are potent stimuli of bone cell proliferation. shear stress; pulsatile fluid flow; osteoblasts (RE)MODELING OF BONE in the skeletal system is strongly influenced by mechanical loading and unloading. Exercise has been shown to stimulate increases in bone mass (24), whereas prolonged mechanical unloading results in bone atrophy (36,45). It has been hypothesized that exercise-induced (re)modeling of bone may result from stimulation of osteoblasts by interstitial fluid flow (IFF) through the porous structure of bone (10, 31). Interstitial fluid flows radially outward through the bone cortex and is driven by hydrostatic pressure gradients across the cortex and pressure gradients from mechanical loading (21,23,39,42). Theoretical models of IFF indicate significant fluid shear stresses in the canaliculi ranging between 6 and 30 dyn/cm 2 (44). During physical activity, rapid dynamic changes in mechanical loading cause transient changes in bone marrow pressure and IFF (30, 43). Rapid changes in IFF subject bone cells to large temporal gradients in interstitial fluid shear stress. Temporal shear stress gradients are defined as the rapid change in shear stress over a small period of time (Ͻ0.5 s) at any given location on the cell surface. Steady shear stress is devoid of temporal gradients and can be established if the onset and/or cessation of flow is slowly transitioned. In any given system of flow, if the change in flow is sudden, significant temporal gradients are generated (8,46). Given that similar temporal gradients in shear stress in other cell types have been shown to be promitogenic compared with steady fluid flow (2), repeated temporal gradients in shear stress through the bone matrix may also stimulate osteoblast proliferation (10, 43).A number of investigators have demonstrated that IFF stimulates elaborate mechanochemical signaling cascades in osteoblasts. Fluid shear has been shown to stimulate osteoblast production and release of cAMP, prostaglandin E 2 (PGE 2 ), inositol triphosphate, and nitric oxide ...

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Section: Discussionmentioning

confidence: 99%

Temporal gradients in shear stimulate osteoblastic proliferation via ERK1/2 and retinoblastoma protein

Jiang

White

Stevens

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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“…An important early response to mechanical loading is the influx of calcium ions. The calcium release may occur directly via mechanosensitive ion channels in the plasma membrane which induce release of calcium from internal stores [18,[35][36][37][38][39]. Calcium release can also occur indirectly via the opening of hemichannels (un-apposed haves of gap junctions) that result in release of ATP and NAD + , which in turn raise the intracellular calcium levels amplifying the wave propagation of calcium [40,41].…”

Section: Key Signaling Molecules In Mechanotransduction: No Prostaglmentioning

confidence: 99%

The role of osteocytes in bone mechanotransduction

2009

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“…production [11][12][13] and the release of signalling molecules such as nitric oxide (NO) and prostaglandin E 2 , when subjected to various flow regimes [4,7,12,14,15]. While such in vitro experiments have identified key mechanisms involved in the mechanotransduction process, the exact mechanical stimulus being imparted to cells within a monolayer is unknown [16] and it is not clear whether the mechanical stimulation is comparable between different experimental systems or, more importantly, is representative of physiological loading conditions experienced by bone cells in vivo.…”

Section: Introductionmentioning

confidence: 99%

A fluid–structure interaction model to characterize bone cell stimulation in parallel-plate flow chamber systems

Vaughan

Haugh

McNamara

2013

J. R. Soc. Interface.

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Bone continuously adapts its internal structure to accommodate the functional demands of its mechanical environment and strain-induced flow of interstitial fluid is believed to be the primary mediator of mechanical stimuli to bone cells in vivo. In vitro investigations have shown that bone cells produce important biochemical signals in response to fluid flow applied using parallel-plate flow chamber (PPFC) systems. However, the exact mechanical stimulus experienced by the cells within these systems remains unclear. To fully understand this behaviour represents a most challenging multi-physics problem involving the interaction between deformable cellular structures and adjacent fluid flows. In this study, we use a fluid-structure interaction computational approach to investigate the nature of the mechanical stimulus being applied to a single osteoblast cell under fluid flow within a PPFC system. The analysis decouples the contribution of pressure and shear stress on cellular deformation and for the first time highlights that cell strain under flow is dominated by the pressure in the PPFC system rather than the applied shear stress. Furthermore, it was found that strains imparted on the cell membrane were relatively low whereas significant strain amplification occurred at the cell -substrate interface. These results suggest that strain transfer through focal attachments at the base of the cell are the primary mediators of mechanical signals to the cell under flow in a PPFC system. Such information is vital in order to correctly interpret biological responses of bone cells under in vitro stimulation and elucidate the mechanisms associated with mechanotransduction in vivo.

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What is the role of the convective current density in the real-time calcium response of cultured bone cells to fluid flow?

Cited by 72 publications

References 21 publications

Temporal gradients in shear stimulate osteoblastic proliferation via ERK1/2 and retinoblastoma protein

Temporal gradients in shear stimulate osteoblastic proliferation via ERK1/2 and retinoblastoma protein

The role of osteocytes in bone mechanotransduction

A fluid–structure interaction model to characterize bone cell stimulation in parallel-plate flow chamber systems

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