A FLUID FLOW RESPONSE DEFICIENCY OF OSTEOPONTIN KNOCK-OUT LONG BONE CELLS

2002 ◽  
Author(s):  
Christian C. Kazanecki ◽  
Larry W. Fisher ◽  
Esben S. Sorensen ◽  
David T. Denhardt
Keyword(s):  
Fluid Flow ◽  
Bone Cells ◽  
Long Bone ◽  
Knock Out ◽  
Flow Response

Induction of NO and prostaglandin E2 in osteoblasts by wall-shear stress but not mechanical strain

1997 ◽  
Vol 273 (4) ◽  
pp. E751-E758 ◽  
Author(s):  
R. Smalt ◽  
F. T. Mitchell ◽  
R. L. Howard ◽  
T. J. Chambers
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Wall Shear Stress ◽  
Bone Cells ◽  
Mechanical Strain ◽  
Osteoblastic Cells ◽  
Long Bone ◽  
Shear Stresses ◽  
No Production ◽  
Wall Shear

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.

scholarly journals The Effect of Fluid Flow Shear Stress and Substrate Stiffness on Yes-Associated Protein (YAP) Activity and Osteogenesis in Murine Osteosarcoma Cells

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3128
Author(s):  
Thomas R. Coughlin ◽  
Ali Sana ◽  
Kevin Voss ◽  
Abhilash Gadi ◽  
Upal Basu-Roy ◽  
...  
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Bone Cells ◽  
Bone Cancer ◽  
Substrate Stiffness ◽  
Flow Shear ◽  
Fluid Movement ◽  
Flow Shear Stress ◽  
Fluid Flow Shear Stress ◽  
New Treatments

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.

Measurement of Osteocyte Deformation Resulting From Fluid Flow Induced Shear Stress

1999 ◽  
Author(s):  
Daniel P. Nicolella ◽  
Eugene Sprague ◽  
Lynda Bonewald
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Flow Rate ◽  
Bone Cells ◽  
Individual Cell ◽  
Analysis Techniques ◽  
Sheer Stress ◽  
Increased Sensitivity ◽  
Cell Strains ◽  
Substrate Strain

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.

scholarly journals Blood flow to long bones indicates activity metabolism in mammals, reptiles and dinosaurs

2011 ◽  
Vol 279 (1728) ◽  
pp. 451-456 ◽  
Author(s):  
Roger S. Seymour ◽  
Sarah L. Smith ◽  
Craig R. White ◽  
Donald M. Henderson ◽  
Daniela Schwarz-Wings
Keyword(s):  
Blood Flow ◽  
Body Size ◽  
Metabolic Rate ◽  
Bone Cells ◽  
Bone Remodelling ◽  
Resting Metabolic Rate ◽  
Blood Flow Rate ◽  
Whole Body ◽  
Long Bone ◽  
Cross Sectional

The cross-sectional area of a nutrient foramen of a long bone is related to blood flow requirements of the internal bone cells that are essential for dynamic bone remodelling. Foramen area increases with body size in parallel among living mammals and non-varanid reptiles, but is significantly larger in mammals. An index of blood flow rate through the foramina is about 10 times higher in mammals than in reptiles, and even higher if differences in blood pressure are considered. The scaling of foramen size correlates well with maximum whole-body metabolic rate during exercise in mammals and reptiles, but less well with resting metabolic rate. This relates to the role of blood flow associated with bone remodelling during and following activity. Mammals and varanid lizards have much higher aerobic metabolic rates and exercise-induced bone remodelling than non-varanid reptiles. Foramen areas of 10 species of dinosaur from five taxonomic groups are generally larger than from mammals, indicating a routinely highly active and aerobic lifestyle. The simple measurement holds possibilities offers the possibility of assessing other groups of extinct and living vertebrates in relation to body size, behaviour and habitat.

Mechanically Induced Calcium Release From Bone Matrix Triggers Intracellular Ca2+ Signalling in Osteoblasts: A Novel Mechanotransduction Mechanism

2011 ◽  
Author(s):  
Xuanhao Sun ◽  
Vipuil Kishore ◽  
Kateri Fites ◽  
Ozan Akkus
Keyword(s):  
Fluid Flow ◽  
Hydrostatic Pressure ◽  
Calcium Release ◽  
Bone Cells ◽  
Bone Matrix ◽  
Bone Adaptation ◽  
Exact Form ◽  
Flow Shear ◽  
Damage Repair ◽  
Physical Stimuli

Bone cells are responsible for sensing and converting the mechanical signals into cellular signals to drive bone adaptation and damage repair [1]. Cell-mediated repair of bone is reported to be in preferential association with regions filled with microdamage [2]. Although different theories have been proposed for mechanisms involved in those processes (such as substrate deformation, fluid flow shear, and hydrostatic pressure in mechanotransduction [3], or microcrack and osteocyte apoptosis in damage detection [4]), knowledge on the exact form of physical stimuli which trigger bone cells, especially in critically loaded regions of bone, is still elusive.

Interactive effects of PTH and mechanical stress on nitric oxide and PGE2 production by primary mouse osteoblastic cells

2003 ◽  
Vol 285 (3) ◽  
pp. E608-E613 ◽  
Author(s):  
Astrid D. Bakker ◽  
Manon Joldersma ◽  
Jenneke Klein-Nulend ◽  
Elisabeth H. Burger
Keyword(s):  
Nitric Oxide ◽  
Fluid Flow ◽  
Bone Formation ◽  
Mechanical Stress ◽  
Bone Cells ◽  
Osteoblastic Cells ◽  
Prostaglandin E ◽  
No Production ◽  
Simultaneous Application ◽  
Primary Mouse

Parathyroid hormone (PTH) and mechanical stress both stimulate bone formation but have opposite effects on bone resorption. PTH increased loading-induced bone formation in a rat model, suggesting that there is an interaction of these stimuli, possibly at the cellular level. To investigate whether PTH can modulate mechanotransduction by bone cells, we examined the effect of 10-9 M human PTH-(1-34) on fluid flow-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production by primary mouse osteoblastic cells in vitro. Mechanical stress applied by means of a pulsating fluid flow (PFF; 0.6 ± 0.3 Pa at 5 Hz) stimulated both NO and PGE2 production twofold. In the absence of stress, PTH also caused a twofold increase in PGE2 production, but NO release was not affected and remained low. Simultaneous application of PFF and PTH nullified the stimulating effect of PFF on NO production, whereas PGE2 production was again stimulated only twofold. Treatment with PTH alone reduced NO synthase (NOS) enzyme activity to undetectable levels. We speculate that PTH prevents stress-induced NO production via the inhibition of NOS, which will also inhibit the NO-mediated upregulation of PGE2 by stress, leaving only the NO-independent PGE2 upregulation by PTH. These results suggest that mechanical loading and PTH interact at the level of mechanotransduction.

scholarly journals Cells Derived from Human Long Bone Appear More Differentiated and More Actively Stimulate Osteoclastogenesis Compared to Alveolar Bone-Derived Cells

2020 ◽  
Vol 21 (14) ◽  
pp. 5072
Author(s):  
Cindy Kelder ◽  
Cornelis J. Kleverlaan ◽  
Marjolijn Gilijamse ◽  
Astrid D. Bakker ◽  
Teun J. de Vries
Keyword(s):  
Tissue Engineering ◽  
Mononuclear Cells ◽  
Alveolar Bone ◽  
Bone Cells ◽  
Transmembrane Protein ◽  
Cell Types ◽  
Long Bone ◽  
Long Bones ◽  
Peripheral Blood Mononuclear ◽  
Alveolar Bone Cells

Osteoblasts derived from mouse skulls have increased osteoclastogenic potential compared to long bone osteoblasts when stimulated with 1,25(OH)2 vitamin D3 (vitD3). This indicates that bone cells from specific sites can react differently to biochemical signals, e.g., during inflammation or as emitted by bioactive bone tissue-engineering constructs. Given the high turn-over of alveolar bone, we hypothesized that human alveolar bone-derived osteoblasts have an increased osteogenic and osteoclastogenic potential compared to the osteoblasts derived from long bone. The osteogenic and osteoclastogenic capacity of alveolar bone cells and long bone cells were assessed in the presence and absence of osteotropic agent vitD3. Both cell types were studied in osteogenesis experiments, using an osteogenic medium, and in osteoclastogenesis experiments by co-culturing osteoblasts with peripheral blood mononuclear cells (PBMCs). Both osteogenic and osteoclastic markers were measured. At day 0, long bones seem to have a more late-osteoblastic/preosteocyte-like phenotype compared to the alveolar bone cells as shown by slower proliferation, the higher expression of the matrix molecule Osteopontin (OPN) and the osteocyte-enriched cytoskeletal component Actin alpha 1 (ACTA1). This phenotype was maintained during the osteogenesis assays, where long bone-derived cells still expressed more OPN and ACTA1. Under co-culture conditions with PBMCs, long bone cells also had a higher Tumor necrose factor-alfa (TNF-α) expression and induced the formation of osteoclasts more than alveolar bone cells. Correspondingly, the expression of osteoclast genes dendritic cell specific transmembrane protein (DC-STAMP) and Receptor activator of nuclear factor kappa-Β ligand (RankL) was higher in long bone co-cultures. Together, our results indicate that long bone-derived osteoblasts are more active in bone-remodeling processes, especially in osteoclastogenesis, than alveolar bone-derived cells. This indicates that tissue-engineering solutions need to be specifically designed for the site of application, such as defects in long bones vs. the regeneration of alveolar bone after severe periodontitis.

scholarly journals A Semi-3D Real-Time Imaging Technique for Measuring Bone Cell Deformation Under Fluid Flow

2009 ◽  
Author(s):  
Andrew D. Baik ◽  
X. Lucas Lu ◽  
Bo Huo ◽  
X. Sherry Liu ◽  
Cheng Dong ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Real Time ◽  
Bone Cells ◽  
Imaging Technique ◽  
Shear Loading ◽  
Cell Deformation ◽  
Directional Information ◽  
Biochemical Pathways ◽  
Volume Dilatation ◽  
A Cell

Bone cells respond to fluid shear loading by activating various biochemical pathways, mediating a dynamic process of bone formation and resorption. The whole-cell volume dilatation [1] and regional deformation of intracellular structures [2] may be able to directly activate and modulate relevant biochemical pathways. Therefore, understanding how bone cells deform under fluid flow can help elucidate the fundamental mechanisms by which mechanical stimuli are able to initiate biochemical responses. Most studies on cell deformation have focused only on cell deformation in the plane parallel to the substrate surface. Height-dependent cell deformation has not been well characterized even though it may contribute greatly to mechanotransduction mechanisms. Traditional techniques to obtain this additional height information of a cell-body, such as confocal and deconvolution microscopy, are inherently limited by the timescale under which the deformational information can be visualized. Previous studies have investigated cell adhesion to substrate under flow using a single view side-view imaging technique [3, 4]. In this study, we present a novel technique that is able to image a single cell simultaneously in two orthogonal planes to obtain real-time images of a cell at a millisecond timescale. Thus, the objectives of this study were to: (1) develop an imaging technique to visualize the depth-directional information of a cell simultaneously with the traditional 2D view; (2) map out the strain fields of the cell by image analysis; and (3) investigate the viscoelastic behavior of osteoblasts under steady fluid flow.

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