scholarly journals Roles of gap junctions and hemichannels in bone cell functions and in signal transmission of mechanical stress

10.2741/2159 ◽  
2007 ◽  
Vol 12 (1) ◽  
pp. 1450 ◽  
Author(s):  
Jean Xin Jiang
Author(s):  
Bo Huo ◽  
Xin L. Lu ◽  
X. Edward Guo

In the present study, the mechanism of intercellular calcium wave propagation in bone cell networks was identified. By using micro-contact printing and self-assembled monolayer technologies, two types of in vitro bone cell networks were constructed: open-ended linear chains and looped hexagonal networks with precisely controlled intercellular distances. Intracellular calcium responses of the cells were recorded and analysed when a single cell in the network was mechanically stimulated by nano-indentation. The looped cell network was shown to be more efficient than the linear pattern in transferring calcium signals from cell to cell. This phenomenon was further examined by pathway-inhibition studies. Intercellular calcium wave propagation was significantly impeded when extracellular adenosine triphosphate (ATP) in the medium was hydrolysed. Chemical uncoupling of gap junctions, however, did not significantly decrease the transferred distance of the calcium wave in the cell networks. Thus, it is extracellular ATP diffusion, rather than molecular transport through gap junctions, that dominantly mediates the transmission of mechanically elicited intercellular calcium waves in bone cells. The inhibition studies also demonstrated that the mechanical stimulation-induced calcium responses required extracellular calcium influx, whereas the ATP-elicited calcium wave relied on calcium release from the calcium store of the endoplasmic reticulum.


2014 ◽  
Vol 20 (6) ◽  
pp. 490-498 ◽  
Author(s):  
C. De Maria ◽  
L. Grassi ◽  
F. Vozzi ◽  
A. Ahluwalia ◽  
G. Vozzi

Purpose – This paper aims to develop a novel micro-ablation system to realise micrometric and well-defined hydrogel structures. To engineer a tissue it is necessary to evaluate several aspects, such as cell-cell and cell-substrate interactions, its micro-architecture and mechanical stimuli that act on it. For this reason, it is important to fabricate a substrate which presents a microtopology similar to natural tissue and has chemical and mechanical properties able to promote cell functions. In this paper, well-defined hydrogel structures embedding cells were microfabricated using a purposely developed technique, micro-laser ablation, based on a thulium laser. Its working parameters (laser power emission, stepper motor velocity) were optimised to produce shaded “serpentine” pattern on a hydrogel film. Design/methodology/approach – In this study, initially, swelling/contraction tests on agarose and alginate hydrogel in different solutions of main components of cell culture medium were performed and were compared with the MECpH model. This comparison matched with good approximation experimental measurements. Once known how hydrogel changed its topology, microstructures with a well-defined topology were realised using a purposely developed micro-laser ablation system design. S5Y5 neuroblastoma cell lines were embedded in hydrogel matrix and the whole structure was ablated with a laser microfabrication system. The cells did not show damages due to mechanical stress present in the hydrogel matrix and to thermal increase induced by the laser beam. Findings – The hydrogel structure is able to reproduce extracellular matrix. Initially, the hydrogel swelling/contraction in different solutions, containing the main components of the most common cell culture media, was analysed. This analysis is important to evaluate if cell culture environment could alter microtopology of realised structures. Then, the same topology was realised on hydrogel film embedding neuronal cells and the cells did not show damages due to mechanical stress present in the hydrogel matrix and to thermal increase induced by the laser beam. The interesting obtained results could be useful to realise well-defined microfabricated hydrogel structures embedding cells to guide tissue formation Originality/value – The originality of this paper is the design and realisation of a 3D microfabrication system able to microfabricate hydrogel matrix embedding cells without inducing cell damage. The ease of use of this system and its potential modularity render this system a novel potential device for application in tissue engineering and regenerative medicine area.


2003 ◽  
Vol 55 (2-3) ◽  
pp. 153-158 ◽  
Author(s):  
Tanja Barkhausen ◽  
Martijn van Griensven ◽  
Johannes Zeichen ◽  
Ulrich Bosch

Physiology ◽  
2013 ◽  
Vol 28 (6) ◽  
pp. 404-413 ◽  
Author(s):  
Béla Suki ◽  
Susumu Sato ◽  
Harikrishnan Parameswaran ◽  
Margit V. Szabari ◽  
Ayuko Takahashi ◽  
...  

Transpulmonary pressure and the mechanical stresses of breathing modulate many essential cell functions in the lung via mechanotransduction. We review how mechanical factors could influence the pathogenesis of emphysema. Although the progression of emphysema has been linked to mechanical rupture, little is known about how these stresses alter lung remodeling. We present possible new directions and an integrated multiscale view that may prove useful in finding solutions for this disease.


Author(s):  
Xiaoling Liao ◽  
Wenfeng Xu ◽  
Bo Li ◽  
Taifu Li ◽  
Ya Fu ◽  
...  
Keyword(s):  

2004 ◽  
Vol 15 (5) ◽  
pp. 581-588 ◽  
Author(s):  
Emmanuel Soffer ◽  
Jean-Pierre Ouhayoun ◽  
Christine Dosquet ◽  
Alain Meunier ◽  
Fani Anagnostou
Keyword(s):  

2019 ◽  
Author(s):  
Nathalie Alexandra Vladis ◽  
Katharina Elisabeth Fischer ◽  
Eva Digalaki ◽  
Daniel-Cosmin Marcu ◽  
Modestos Nakos Bimpos ◽  
...  

AbstractThe nervous system is a central regulator of longevity, but how neuronal communication interfaces with ageing pathways is not well understood. Gap junctions are key conduits that allow voltage and metabolic signal transmission across cellular networks, yet it has remained unexplored whether they play a role in regulating ageing and longevity. We show that the innexin genes encoding gap junction subunits in Caenorhabditis elegans have extensive and diverse impacts on lifespan. Loss of the neural innexin unc-9 increases longevity by a third and also strongly benefits healthspan. Unc-9 acts specifically in a glutamatergic circuit linked to mechanosensation. Absence of unc-9 depends on a functional touch-sensing machinery to regulate lifespan and alters the age-dependent decline of mechanosensory neurons. The life extension produced by removal of unc-9 requires reactive oxygen species. Our work reveals for the first time that gap junctions are important regulators of ageing and lifespan.


Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1576
Author(s):  
Diana Cheshmedzhieva ◽  
Sonia Ilieva ◽  
Eugene A. Permyakov ◽  
Sergei E. Permyakov ◽  
Todor Dudev

The extracellular calcium-sensing receptor (CaSR) controls vital bone cell functions such as cell growth, differentiation and apoptosis. The binding of the native agonist (Ca2+) to CaSR activates the receptor, which undergoes structural changes that trigger a cascade of events along the cellular signaling pathways. Strontium (in the form of soluble salts) has been found to also be a CaSR agonist. The activation of the receptor by Sr2+ is considered to be the major mechanism through which strontium exerts its anti-osteoporosis effect, mostly in postmenopausal women. Strontium-activated CaSR initiates a series of signal transduction events resulting in both osteoclast apoptosis and osteoblast differentiation, thus strengthening the bone tissue. The intimate mechanism of Sr2+ activation of CaSR is still enigmatic. Herewith, by employing a combination of density functional theory (DFT) calculations and polarizable continuum model (PCM) computations, we have found that the Ca2+ binding sites 1, 3, and 4 in the activated CaSR, although possessing a different number and type of protein ligands, overall structure and charge state, are all selective for Ca2+ over Sr2+. The three binding sites, regardless of their structural differences, exhibit almost equal metal selectivity if they are flexible and have no geometrical constraints on the incoming Sr2+. In contrast to Ca2+ and Sr2+, Mg2+ constructs, when allowed to fully relax during the optimization process, adopt their stringent six-coordinated octahedral structure at the expense of detaching a one-backbone carbonyl ligand and shifting it to the second coordination layer of the metal. The binding of Mg2+ and Sr2+ to a rigid/inflexible calcium-designed binding pocket requires an additional energy penalty for the binding ion; however, the price for doing so (to be paid by Sr2+) is much less than that of Mg2+. The results obtained delineate the key factors controlling the competition between metal cations for the receptor and shed light on some aspects of strontium’s therapeutic effects.


Author(s):  
Danese M. Joiner ◽  
Ethan L. H. Daley ◽  
Steven A. Goldstein

It is well established that bone can adapt to the demands of daily mechanical usage. Mechanical loading can result in bone formation depending on the magnitude, duration, and frequency. Unloading, which can occur during bed rest, micro-gravity exposure and a variety of clinical conditions, can result in bone resorption. In vitro studies have demonstrated that osteoblasts and osteocytes respond to mechanical stimulation, especially oscillatory fluid shear stress. Mechano-responses have included increases in inter- and intra-cellular communication through gap junctions and soluble factors such as nitric oxide and prostaglandin E2 [1]. Bone cell gap junctions are primarily comprised of connexin 43 (Cx43). Mice lacking Cx43 have an osteopenic phenotype and when subjected to cyclic 4 pt. bending loads have an increased tibia bone marrow area [2, 3]. These observations may represent altered cell signaling. To investigate the role of Cx43 in cell signaling and bone mechanotransduction the Cx43 gene was silenced in MC3T3-E1 pre-osteoblast cells subjected to oscillatory fluid shear stress.


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