Influence of increased mechanical loading by hypergravity on the microtubule cytoskeleton and prostaglandin E2 release in primary osteoblasts

2005 ◽  
Vol 289 (1) ◽  
pp. C148-C158 ◽  
Author(s):  
Nancy D. Searby ◽  
Charles R. Steele ◽  
Ruth K. Globus

Cells respond to a wide range of mechanical stimuli such as fluid shear and strain, although the contribution of gravity to cell structure and function is not understood. We hypothesized that bone-forming osteoblasts are sensitive to increased mechanical loading by hypergravity. A centrifuge suitable for cell culture was developed and validated, and then primary cultures of fetal rat calvarial osteoblasts at various stages of differentiation were mechanically loaded using hypergravity. We measured microtubule network morphology as well as release of the paracrine factor prostaglandin E2 (PGE2). In immature osteoblasts, a stimulus of 10× gravity (10 g) for 3 h increased PGE2 2.5-fold and decreased microtubule network height 1.12-fold without affecting cell viability. Hypergravity (3 h) caused dose-dependent (5–50 g) increases in PGE2 (5.3-fold at 50 g) and decreases (1.26-fold at 50 g) in microtubule network height. PGE2 release depended on duration but not orientation of the hypergravity load. As osteoblasts differentiated, sensitivity to hypergravity declined. We conclude that primary osteoblasts demonstrate dose- and duration-dependent sensitivity to gravitational loading, which appears to be blunted in mature osteoblasts.

2019 ◽  
Vol 20 (9) ◽  
pp. 2260 ◽  
Author(s):  
Hessam Tabeian ◽  
Beatriz F. Betti ◽  
Cinthya dos Santos Cirqueira ◽  
Teun J. de Vries ◽  
Frank Lobbezoo ◽  
...  

The temporomandibular joint (TMJ), which differs anatomically and biochemically from hyaline cartilage-covered joints, is an under-recognized joint in arthritic disease, even though TMJ damage can have deleterious effects on physical appearance, pain and function. Here, we analyzed the effect of IL-1β, a cytokine highly expressed in arthritic joints, on TMJ fibrocartilage-derived cells, and we investigated the modulatory effect of mechanical loading on IL-1β-induced expression of catabolic enzymes. TMJ cartilage degradation was analyzed in 8–11-week-old mice deficient for IL-1 receptor antagonist (IL-1RA−/−) and wild-type controls. Cells were isolated from the juvenile porcine condyle, fossa, and disc, grown in agarose gels, and subjected to IL-1β (0.1–10 ng/mL) for 6 or 24 h. Expression of catabolic enzymes (ADAMTS and MMPs) was quantified by RT-qPCR and immunohistochemistry. Porcine condylar cells were stimulated with IL-1β for 12 h with IL-1β, followed by 8 h of 6% dynamic mechanical (tensile) strain, and gene expression of MMPs was quantified. Early signs of condylar cartilage damage were apparent in IL-1RA−/− mice. In porcine cells, IL-1β strongly increased expression of the aggrecanases ADAMTS4 and ADAMTS5 by fibrochondrocytes from the fossa (13-fold and 7-fold) and enhanced the number of MMP-13 protein-expressing condylar cells (8-fold). Mechanical loading significantly lowered (3-fold) IL-1β-induced MMP-13 gene expression by condylar fibrochondrocytes. IL-1β induces TMJ condylar cartilage damage, possibly by enhancing MMP-13 production. Mechanical loading reduces IL-1β-induced MMP-13 gene expression, suggesting that mechanical stimuli may prevent cartilage damage of the TMJ in arthritic patients.


2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Marta Boccazzi ◽  
Juliette Van Steenwinckel ◽  
Anne-Laure Schang ◽  
Valérie Faivre ◽  
Tifenn Le Charpentier ◽  
...  

AbstractA leading cause of preterm birth is the exposure to systemic inflammation (maternal/fetal infection), which leads to neuroinflammation and white matter injury (WMI). A wide range of cytokines and chemokines are expressed and upregulated in oligodendrocytes (OLs) in response to inflammation and numerous reports show that OLs express several receptors for immune related molecules, which enable them to sense inflammation and to react. However, the role of OL immune response in WMI is unclear. Here, we focus our study on toll-like receptor-3 (TLR3) that is activated by double-strand RNA (dsRNA) and promotes neuroinflammation. Despite its importance, its expression and role in OLs remain unclear. We used an in vivo mouse model, which mimics inflammation-mediated WMI of preterm born infants consisting of intraperitoneal injection of IL-1β from P1 to P5. In the IL-1β-treated animals, we observed the upregulation of Tlr3, IL-1β, IFN-β, Ccl2, and Cxcl10 in both PDGFRα+ and O4+ sorted cells. This upregulation was higher in O4+ immature OLs (immOLs) as compared to PDGFRα+ OL precursor cells (OPCs), suggesting a different sensitivity to neuroinflammation. These observations were confirmed in OL primary cultures: cells treated with TLR3 agonist Poly(I:C) during differentiation showed a stronger upregulation of Ccl2 and Cxcl10 compared to cells treated during proliferation and led to decreased expression of myelin genes. Finally, OLs were able to modulate microglia phenotype and function depending on their maturation state as assessed by qPCR using validated markers for immunomodulatory, proinflammatory, and anti-inflammatory phenotypes and by phagocytosis and morphological analysis. These results show that during inflammation the response of OLs can play an autonomous role in blocking their own differentiation: in addition, the immune activation of OLs may play an important role in shaping the response of microglia during inflammation.


2000 ◽  
Vol 6 (S2) ◽  
pp. 984-985
Author(s):  
Kenneth A. Barbee

Vascular endothelial cells experience a wide range of mechanical stimuli in vivo, including dynamic stretching and time-varying shear stress due to pulsatile blood flow. Under physiologic conditions, these hemodynamic forces constitute an important component of the cells' environment and are necessary for the normal maintenance of the structure and function of the vessel wall. Implantation of artificial vascular graft materials can significantly alter the mechanical environment of the cell. Furthermore, an important design criterion for engineered tissue constructs is the production of a mechanical environment that, ideally, stimulates normal growth and structural adaptation and. At least, avoids extremes in mechanical loading that might cause cellular trauma. In this paper, we investigate the mechanical loading conditions associated with normal and pathological mechanotransduction and cellular injury with an emphasis on the loading rate dependence of the cellular responses.A custom designed cone-and-plate device] allows arbitrary cone velocity waveforms to be generated.


2013 ◽  
Author(s):  
Wenjie Xie ◽  
Silvia Dolder ◽  
Mark Siegrist ◽  
Antoinette Wetterwald ◽  
Willy Hofstetter

2016 ◽  
pp. 126-129
Author(s):  
M. Makarenko ◽  
◽  
D. Hovsyeyev ◽  
L. Sydoryk ◽  
◽  
...  

Different kinds of physiological stress cause mass changes in the cells, including the changes in the structure and function of the protein complexes and in separate molecules. The protein functions is determined by its folding (the spatial conclusion), which depends on the functioning of proteins of thermal shock- molecular chaperons (HSPs) or depends on the stress proteins, that are high-conservative; specialized proteins that are responsible for the correct proteinaceous folding. The family of the molecular chaperones/ chaperonins/ Hsp60 has a special place due to the its unique properties of activating the signaling cascades through the system of Toll-like receptors; it also stimulates the cells to produce anti- inflammatory cytokines, defensins, molecules of cell adhesion and the molecules of MHC; it functions as the intercellular signaling molecule. The pathological role of Hsp60 is established in a wide range of illnesses, from diabetes to atherosclerosis, where Hsp60 takes part in the regulation of both apoptosis and the autoimmune processes. The presence of the HSPs was found in different tissues that are related to the reproductive system. Key words: molecular chaperons (HSPs), Toll-like receptors, reproductive function, natural auto antibody.


2012 ◽  
Vol 6 (1-3) ◽  
pp. 243-259 ◽  
Author(s):  
Yohan Yoo

This article demonstrates the need for the iconic status and function of Buddhist scripture to receive more attention by illuminating how lay Korean Buddhists try to appropriate the power of sutras. The oral and aural aspects of scripture, explained by Wilfred Cantwell Smith, provide only a limited understanding of the characteristics of scripture. It should be noted that, before modern times, most lay people, not only in Buddhist cultures but also in Christian and other traditions, neither had the chance to recite scriptures nor to listen to their recitations regularly. Several clear examples demonstrate contemporary Korean Buddhists’ acceptance of the iconic status of sutras and their attempt to appropriate the power and status of those sacred texts. In contemporary Korea, lay Buddhists try to claim the power of scriptures in their daily lives by repeating and possessing them. Twenty-first century lay believers who cannot read or recite in a traditional style have found new methods of repetition, such as internet programs for copying sacred texts and for playing recordings of their recitations. In addition, many Korean Buddhists consider the act of having sutras in one’s possession to be an effective way of accessing the sacred status and power of these texts. Hence, various ways of possessing them have been developed in a wide range of products, from fancy gilded sutras to sneakers embroidered with mantras.


2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.


Author(s):  
Nugroho Budhiwaluyo ◽  
Rayandra Asyhar ◽  
Bambang Hariyadi

  This research aims to produce a final product in the form of a performance-assessment instrument on Cell Structure and Function experiment. The development model is ADDIE. Based on expert's judgment, the instrument was valid and can be tested in the field. Field-test results shown that the product performs high validity and reliability value on measuring student performance on Cell Structure and Function experiment. Therefore, it is concluded that this performance-assessment instrument theoretically and practically has a good quality for measuring student performance in both process and product performance on Cell Structure and Function experiment. Keywords: Development, Performance-Assessment Instrument, Cell Structure and Function Experiment 


Author(s):  
Erik Gray

Love begets poetry; poetry begets love. These two propositions have seemed evident to thinkers and poets across the Western literary tradition. Plato writes that “anyone that love touches instantly becomes a poet.” And even today, when poetry has largely disappeared from the mainstream of popular culture, it retains its romantic associations. But why should this be so—what are the connections between poetry and erotic love that lead us to associate them so strongly with one another? An examination of different theories of both love and poetry across the centuries reveals that the connection between them is not merely an accident of cultural history—the result of our having grown up hearing, or hearing about, love poetry—but something more intrinsic. Even as definitions of them have changed, the two phenomena have consistently been described in parallel terms. Love is characterized by paradox. Above all, it is both necessarily public, because interpersonal, and intensely private; hence it both requires expression and resists it. In poetry, especially lyric poetry, which features its own characteristic paradoxes and silences, love finds a natural outlet. This study considers both the theories and the love poems themselves, bringing together a wide range of examples from different eras in order to examine the major structures that love and poetry share. It does not aim to be a comprehensive history of Western love poetry, but an investigation into the meaning and function of recurrent tropes, forms, and images employed by poets to express and describe erotic love.


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