Measurement of Osteocyte Deformation Resulting From Fluid Flow Induced Shear Stress

1999 ◽  
Author(s):  
Daniel P. Nicolella ◽  
Eugene Sprague ◽  
Lynda Bonewald

Abstract It has been shown that bone cells are more responsive to fluid flow induced shear stress as compared to applied substrate strain (Owan, et al., 1997, Smalt, et al., 1997). Using novel micromechanical analysis techniques, we have measured individual cell strains resulting from 10 minutes of continuous fluid flow at a flow rate that produces a shear stress of 15 dyne/cm2. Individual cell strains varied widely from less than 1.0% to over 25% strain within the same group of cells. The increased sensitivity of cells to fluid flow induced shear stress may be attributed to much greater cellular deformations resulting from fluid flow induced sheer stress.

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3128
Author(s):  
Thomas R. Coughlin ◽  
Ali Sana ◽  
Kevin Voss ◽  
Abhilash Gadi ◽  
Upal Basu-Roy ◽  
...  

Osteosarcoma (OS) is an aggressive bone cancer originating in the mesenchymal lineage. Prognosis for metastatic disease is poor, with a mortality rate of approximately 40%; OS is an aggressive disease for which new treatments are needed. All bone cells are sensitive to their mechanical/physical surroundings and changes in these surroundings can affect their behavior. However, it is not well understood how OS cells specifically respond to fluid movement, or substrate stiffness—two stimuli of relevance in the tumor microenvironment. We used cells from spontaneous OS tumors in a mouse engineered to have a bone-specific knockout of pRb-1 and p53 in the osteoblast lineage. We silenced Sox2 (which regulates YAP) and tested the effect of fluid flow shear stress (FFSS) and substrate stiffness on YAP expression/activity—which was significantly reduced by loss of Sox2, but that effect was reversed by FFSS but not by substrate stiffness. Osteogenic gene expression was also reduced in the absence of Sox2 but again this was reversed by FFSS and remained largely unaffected by substrate stiffness. Thus we described the effect of two distinct stimuli on the mechanosensory and osteogenic profiles of OS cells. Taken together, these data suggest that modulation of fluid movement through, or stiffness levels within, OS tumors could represent a novel consideration in the development of new treatments to prevent their progression.


1997 ◽  
Vol 273 (4) ◽  
pp. E751-E758 ◽  
Author(s):  
R. Smalt ◽  
F. T. Mitchell ◽  
R. L. Howard ◽  
T. J. Chambers

The nature of the stimulus sensed by bone cells during mechanical usage has not yet been determined. Because nitric oxide (NO) and prostaglandin (PG) production appear to be essential early responses to mechanical stimulation in vivo, we used their production to compare the responsiveness of bone cells to strain and fluid flow in vitro. Cells were incubated on polystyrene film and subjected to unidirectional linear strains in the range 500–5,000 microstrain (με). We found no increase in NO or PGE2 production after loading of rat calvarial or long bone cells, MC3T3-E1, UMR-106–01, or ROS 17/2.8 cells. In contrast, exposure of osteoblastic cells to increased fluid flow induced both PGE2 and NO production. Production was rapidly induced by wall-shear stresses of 148 dyn/cm2 and was observed in all the osteoblastic populations used but not in rat skin fibroblasts. Fluid flow appeared to act through an increase in wall-shear stress. These data suggest that mechanical loading of bone is sensed by osteoblastic cells through fluid flow-mediated wall-shear stress rather than by mechanical strain.


1999 ◽  
Author(s):  
Jun You ◽  
Clare E. Yellowley ◽  
Henry J. Donahue ◽  
Christopher R. Jacobs

Abstract It is believed that bone cells can sense mechanical loading and alter bone external shape and internal structure to efficiently support the load bearing demands placed upon it. However, the mechanism by which bone cells sense and respond to their mechanical environment is still poorly understood. In particular, the load-induced signals to which bone cells respond, e.g. fluid flow, substrate deformation, electrokinetic effects etc., are unclear. Furthermore, there are few studies focused on the effects of physiological strain (strain < 0.5%, Burr, 1996; Owan, 1997) on bone cells. The goal of this study was to investigate cytosolic Ca2+ mobilization (a very early signaling event) in response to different substrate strains (physiological or supra-physiological strains), and to distinguish the effects of substrate strain from those of fluid flow by applying precisely controlled strain without induced fluid flow. In addition, we quantified the effect of physiologically relevant fluid flow (Cowin, 1995) and substrate stretch on the expression of mRNA for the bone matrix protein osteopontin (OPN). A computer controlled stretch device was employed to apply different substrate strains, 0.1%, 1%, 5% and 10%. A parallel plate flow chamber was used to test cell responses to steady and oscillating flows (20dyn/cm2, 1Hz). Our data demonstrate that physiological strain (< 0.5%) does not induce [Ca2+]i responses in primary rat osteoblastic cells (ROB) in vitro. However, there was a significant (p < 0.05) increase in the number of responding cells at supra-physiological strains of 1, 5, and 10% suggesting that the cells were capable of a biological response. Similar results for human fetal osteoblastic cells (hFOB 1.19) and osteocyte-like cells (ML0-Y4) were obtained. Furthermore, compared to physiological substrate deformation, physiological fluid flow induced greater [Ca2+]i responses for hFOB cells, and these [Ca2+]i responses were quantitatively similar to those obtained for 10% substrate strain. Moreover we found no change in osteopontin mRNA expression after 0.5% strain stretch. Conversely, physiological oscillating flow (20dyn/cm2, 1Hz) caused a significant increase in osteopontin mRNA. These data suggest that, relative to fluid flow, substrate deformation may play less of a role in bone cell mechanotransduction.


The present research paper concerns with a two phase fluid flow, consists an acentric plasma layer region free from red cells and a central core region represented by Hershel – Bulkley fluid through a bell shaped stenosed artery. Mathematical expressions for characteristics of blood flow namely core velocity (uc ), peripheral velocity ( up ), shear stress at wall ( ) and total volumetric fluid flow rate (Q) have been estimated and depicted graphically . The effect of shape parameter peripheral layer viscosity, on these characteristics has been depicted with graphs. It has been noticed that the fluid flow rate (Q) and shear stress at wall ( ) decreases as the increases of peripheral layer viscosity.


2013 ◽  
Vol 10 (81) ◽  
pp. 20120900 ◽  
Author(s):  
T. J. Vaughan ◽  
M. G. Haugh ◽  
L. M. McNamara

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 .


2003 ◽  
Vol 36 (9) ◽  
pp. 1363-1371 ◽  
Author(s):  
T.L.Haut Donahue ◽  
T.R. Haut ◽  
C.E. Yellowley ◽  
H.J. Donahue ◽  
C.R. Jacobs
Keyword(s):  

2000 ◽  
Vol 122 (4) ◽  
pp. 387-393 ◽  
Author(s):  
J. You ◽  
C. E. Yellowley ◽  
H. J. Donahue ◽  
Y. Zhang ◽  
Q. Chen ◽  
...  

Although it is well accepted that bone tissue metabolism is regulated by external mechanical loads, it remains unclear to what load-induced physical signals bone cells respond. In this study, a novel computer-controlled stretch device and parallel plate flow chamber were employed to investigate cytosolic calcium Ca2+i mobilization in response to a range of dynamic substrate strain levels (0.1–10 percent, 1 Hz) and oscillating fluid flow (2 N/m2, 1 Hz). In addition, we quantified the effect of dynamic substrate strain and oscillating fluid flow on the expression of mRNA for the bone matrix protein osteopontin (OPN). Our data demonstrate that continuum strain levels observed for routine physical activities (<0.5 percent) do not induce Ca2+i responses in osteoblastic cells in vitro. However, there was a significant increase in the number of responding cells at larger strain levels. Moreover, we found no change in osteopontin mRNA level in response to 0.5 percent strain at 1 Hz. In contrast, oscillating fluid flow predicted to occur in the lacunar–canalicular system due to routine physical activities (2 N/m2, 1 Hz) caused significant increases in both Ca2+i and OPN mRNA. These data suggest that, relative to fluid flow, substrate deformation may play less of a role in bone cell mechanotransduction associated with bone adaptation to routine loads. [S0148-0731(00)01204-8]


In this research paper, fluid flow is considered in uni direction through the multi – irregular constricted artery. Blood has been considered Hershcel –Bulkley i.e. non- Newtonion. Analytical techniques are carried out to solve the problem. Mathematical expressions for several variables of fluid flow has been estabilished. The effect of slip velocity, flow behaviour index and yield stress on axial velocity volumetric flow rate and wall shear stress have been depicted through graphs. It has noticed that velocity in axial direction and fluid flow rate increases as increase in slip velocity at arterial wall. It has also observed that shear stress increases with increasing of yield stress. Flow rate reaches lowest value at some points in the portion of stenosis for clinical investigation.


2001 ◽  
Vol 90 (5) ◽  
pp. 1849-1854 ◽  
Author(s):  
E. A. Nauman ◽  
R. L. Satcher ◽  
T. M. Keaveny ◽  
B. P. Halloran ◽  
D. D. Bikle

Although there is no consensus as to the precise nature of the mechanostimulatory signals imparted to the bone cells during remodeling, it has been postulated that deformation-induced fluid flow plays a role in the mechanotransduction pathway. In vitro, osteoblasts respond to fluid shear stress with an increase in PGE2production; however, the long-term effects of fluid shear stress on cell proliferation and differentiation have not been examined. The goal of this study was to apply continuous pulsatile fluid shear stresses to osteoblasts and determine whether the initial production of PGE2 is associated with long-term biochemical changes. The acute response of bone cells to a pulsatile fluid shear stress (0.6 ± 0.5 Pa, 3.0 Hz) was characterized by a transient fourfold increase in PGE2 production. After 7 days of static culture (0 dyn/cm2) or low (0.06 ± 0.05 Pa, 0.3 Hz) or high (0.6 ± 0.5 Pa, 3.0 Hz) levels of pulsatile fluid shear stress, the bone cells responded with an 83% average increase in cell number, but no statistical difference ( P > 0.53) between the groups was observed. Alkaline phosphatase activity per cell decreased in the static cultures but not in the low- or high-flow groups. Mineralization was also unaffected by the different levels of applied shear stress. Our results indicate that short-term changes in PGE2 levels caused by pulsatile fluid flow are not associated with long-term changes in proliferation or mineralization of bone cells.


2019 ◽  
Vol 11 (1) ◽  
pp. 01025-1-01025-5 ◽  
Author(s):  
N. A. Borodulya ◽  
◽  
R. O. Rezaev ◽  
S. G. Chistyakov ◽  
E. I. Smirnova ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document