280: Primary Cilia and Fluid Flow Establish the Orientation of Mitotic Spindles

2010 ◽  
Vol 55 (4) ◽  
pp. B101
Author(s):  
Neeraj Sharma ◽  
Bradley K. Yoder
Keyword(s):  
Fluid Flow ◽  
Primary Cilia ◽  
Mitotic Spindles

Response of human osteoblast-like cells to fluid flow shear: A potential role for the microtubule network and primary ciliums

2007 ◽  
Vol 30 (4) ◽  
pp. 90 ◽  
Author(s):  
Kenneth A. Myers ◽  
Jerome B. Rattner ◽  
Nigel G. Shrive ◽  
David A. Hart
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Cellular Response ◽  
Primary Cilia ◽  
Cytochalasin D ◽  
Shear Stresses ◽  
Human Osteoblast ◽  
Flow Shear ◽  
Microtubule Network

Introduction: A limited understanding of the cellular mechanisms governing bone mechanotransduction has inhibited the development of clinical treatments for a variety of bone disorders, including osteoporosis, osteoarthritis and microgravity-associated bone atrophy. The cytoskeleton is thought to play a role in cellular mechanotransduction, however the exact mechanism in bone cells has not yet been clearly elucidated. Studies involving cytoskeletal inhibitors have not generally considered secondary effects on cellular organelles such as the primary cilia. These cellular projections could account for the disparity between shear stresses predicted to occur in vivo and the minimum threshold of membrane deformation required to elicit a cellular response in vitro. Methods: MG-63 (human osteoblast-like) cells were cultured in vitro. Cultures were exposed to intermittent cyclic fluid flow shear stress (1 Pa amplitude), for 8 or 12 hrs. Some cultures were loaded in the presence of nocodazole (a microtubule inhibitor) or cytochalasin D (an actin filament inhibitor). The cellular response was analyzed through RT-PCR assessment of messenger RNA levels for specific molecules related to matrix metabolism. The effects of drug treatments on cytoskeletal disorganization and the primary cilia were assessed with immunocytochemistry and electron microscopy. Results: In untreated cultures, shear stress was associated with significant increases in mRNA levels for collagen I and matrix metalloproteinases 1 and 3, for both time points assessed. These increases were maintained in cultures loaded in the presence of cytochalasin D, but were almost completely abrogated in nocodazole-treated cultures. Cytoskeletal inhibitors exerted some dose-dependent effects on length and structure of primary cilia in MG-63 cells. Conclusions: The microtubule network appears to be necessary for some shear-induced responses of osteoblast-like cells. MG-63 cells possess primary cilia, organelles that could amplify fluid flow shear, accounting for some apparent contradictions between studies related to osteoblast mechanosensitivity. Since these structures are composed of microtubules, the observation that microtubule disruptors inhibit the shear response of osteoblast-like cells suggests the primary cilium may have a role in osteoblast mechanotransduction. The effects of cytoskeletal inhibitors on cilium structure may explain the conflicting results of earlier mechanotransduction studies.

scholarly journals Oscillatory fluid flow influences primary cilia and microtubule mechanics

Cytoskeleton ◽  
2014 ◽  
Vol 71 (7) ◽  
pp. 435-445 ◽  
Author(s):  
Lina C. Espinha ◽  
David A. Hoey ◽  
Paulo R. Fernandes ◽  
Hélder C. Rodrigues ◽  
Christopher R. Jacobs
Keyword(s):  
Fluid Flow ◽  
Primary Cilia

Mechanical properties of primary cilia regulate the response to fluid flow

2010 ◽  
Vol 298 (5) ◽  
pp. F1096-F1102 ◽  
Author(s):  
Susanna Rydholm ◽  
Gordon Zwartz ◽  
Jacob M. Kowalewski ◽  
Padideh Kamali-Zare ◽  
Thomas Frisk ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Fluid Flow ◽  
Calcium Signaling ◽  
Mammalian Cells ◽  
Primary Cilia ◽  
Cyst Formation ◽  
Calcium Signal ◽  
Autosomal Dominant Polycystic Kidney ◽  
Stress Buildup ◽  
Surrounding Membrane

The primary cilium is a ubiquitous organelle present on most mammalian cells. Malfunction of the organelle has been associated with various pathological disorders, many of which lead to cystic disorders in liver, pancreas, and kidney. Primary cilia have in kidney epithelial cells been observed to generate intracellular calcium in response to fluid flow, and disruption of proteins involved in this calcium signaling lead to autosomal dominant polycystic kidney disease, implying a direct connection between calcium signaling and cyst formation. It has also been shown that there is a significant lag between the onset of flow and initiation of the calcium signal. The present study focuses on the mechanics of cilium bending and the resulting calcium signal. Visualization of real-time cilium movements in response to different types of applied flow showed that the bending is fast compared with the initiation of calcium increase. Mathematical modeling of cilium and surrounding membrane was performed to deduce the relation between bending and membrane stress. The results showed a delay in stress buildup that was similar to the delay in calcium signal. Our results thus indicate that the delay in calcium response upon cilia bending is caused by mechanical properties of the cell membrane.

Primary Cilia Mediate Intracellular cAMP Responses in Bone Cells Exposed to Dynamic Fluid Flow

2008 ◽  
Author(s):  
Ronald Y. Kwon ◽  
Sara Temiyasathit ◽  
Padmaja Tummala ◽  
Clarence Quah ◽  
Christopher R. Jacobs
Keyword(s):  
Fluid Flow ◽  
Primary Cilia ◽  
Bone Structure ◽  
Bone Cells ◽  
Cyclic Adenosine Monophosphate ◽  
Second Messenger ◽  
Adenosine Monophosphate ◽  
Cell Types ◽  
Intracellular Camp ◽  
And Function

It is well accepted that fluid flow is an important mechanical signal in regulating bone structure and function. Primary cilia, which are non-motile, microtubule based organelles that extend from the centrosome and project into extracellular space in many cell types, have recently been shown to mediate fluid flow-induced osteogenic responses in MLO-Y4 osteocyte-like cells [1]. However, primary cilia did not mediate increases in intracellular Ca2+ concentration, and the second messenger system(s) involved in primary cilia-mediated mechanosensing has yet to be elucidated. In this study, our goals were to (1) determine whether exposing bone cells to oscillatory fluid flow modulates intracellular levels of cyclic adenosine monophosphate (cAMP), another ubiquitous second messenger molecule, and (2) investigate whether this modulation may be mediated by primary cilia.

scholarly journals An experimental and computational analysis of primary cilia deflection under fluid flow

2012 ◽  
Vol 17 (1) ◽  
pp. 2-10 ◽  
Author(s):  
Matthew E. Downs ◽  
An M. Nguyen ◽  
Florian A. Herzog ◽  
David A. Hoey ◽  
Christopher R. Jacobs
Keyword(s):  
Fluid Flow ◽  
Primary Cilia ◽  
Computational Analysis

OSCILLATORY FLUID FLOW INFLUENCES THE NUMBER OF MICROTUBULES ATTACHED TO THE BASE OF PRIMARY CILIA

2012 ◽  
Vol 45 ◽  
pp. S446
Author(s):  
Lina C. Espinha ◽  
David A. Hoey ◽  
Christopher R. Jacobs
Keyword(s):  
Fluid Flow ◽  
Primary Cilia
Sign in / Sign up

Export Citation Format

Share Document