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del Fattore A.,Regenerative Medicine Unit | Teti A.,University of LAquila
Inflammation and Allergy - Drug Targets | Year: 2012

Osteoimmunology is an interdisciplinary field addressing the interplay between the skeletal and the immune system. A substantial body of evidence demonstrated the existence of two-way regulatory mechanisms that affect both systems, placing them in much closer association to each other than one could ever predict. Inflammatory diseases have long been known to induce alterations in bone metabolism, and inflammatory cytokines play prominent roles in the control of bone resorption, representing communication pathways bridging the two systems. Osteoclasts are particularly linked to the immune cells because they belong to the monocyte/macrophage family, have tight relationships with B and T cells, and differentiate in response to RANKL which is also produced by lymphocytes and regulates lymphopoiesis. Osteoclasts are negatively regulated by cytokines and other factors known for their anti-inflammatory and immune regulatory activity. Finally, they express immune co-receptor typical of immune cells which are indispensable for their differentiation, thus leading to the hypothesis that osteoclasts are immune cells themselves. The underlying principle why an immune cell is required to resorb bone has not yet been elucidated. Data from early literature suggest that the bone matrix could trigger an innate immune response activating giant cells that could destroy large bone areas because of their unique property of resorbing bone extracellularly. Bone resorption could though be prevented by the physical barrier made by osteoblasts and lining cells, whose retraction would be required to give access to osteoclasts when specific pathways signal their precursors to differentiate and mature osteoclasts to reach the uncovered bone surface. © 2012 Bentham Science Publishers.


Cappariello A.,Regenerative Medicine Unit | Maurizi A.,University of LAquila | Veeriah V.,University of LAquila | Veeriah V.,Anna University | Teti A.,University of LAquila
Archives of Biochemistry and Biophysics | Year: 2014

Much has been written recently on osteoclast biology, but this cell type still astonishes scientists with its multifaceted functions and unique properties. The last three decades have seen a change in thinking about the osteoclast, from a cell with a single function, which just destroys the tissue it belongs to, to an "orchestrator" implicated in the concerted regulation of bone turnover. Osteoclasts have unique morphological features, organelle distribution and plasma membrane domain organization. They require polarization to cause extracellular bone breakdown and release of the digested bone matrix products into the circulation. Osteoclasts contribute to the control of skeletal growth and renewal. Alongside other organs, including kidney, gut, thyroid and parathyroid glands, they also affect calcemia and phosphatemia. Osteoclasts are very sensitive to pro-inflammatory stimuli, and studies in the '00s ascertained their tight link with the immune system, bringing about the question why bone needs a cell regulated by the immune system to remove the extracellular matrix components. Recently, osteoclasts have been demonstrated to contribute to the hematopoietic stem cell niche, controlling local calcium concentration and regulating the turnover of factors essential for hematopoietic stem cell mobilization. Finally, osteoclasts are important regulators of osteoblast activity and angiogenesis, both by releasing factors stored in the bone matrix, and secreting "clastokines" that regulate the activity of neighboring cells. All these facets will be discussed in this review article, with the aim of underscoring The Great Beauty of the osteoclast. © 2014 Elsevier Inc. All rights reserved.


Cappariello A.,Regenerative Medicine Unit | Maurizi A.,University of LAquila | Veeriah V.,University of LAquila | Veeriah V.,Anna University | Teti A.,University of LAquila
Archives of Biochemistry and Biophysics | Year: 2014

Much has been written recently on osteoclast biology, but this cell type still astonishes scientists with its multifaceted functions and unique properties. The last three decades have seen a change in thinking about the osteoclast, from a cell with a single function, which just destroys the tissue it belongs to, to an "orchestrator" implicated in the concerted regulation of bone turnover. Osteoclasts have unique morphological features, organelle distribution and plasma membrane domain organization. They require polarization to cause extracellular bone breakdown and release of the digested bone matrix products into the circulation. Osteoclasts contribute to the control of skeletal growth and renewal. Alongside other organs, including kidney, gut, thyroid and parathyroid glands, they also affect calcemia and phosphatemia. Osteoclasts are very sensitive to pro-inflammatory stimuli, and studies in the '00s ascertained their tight link with the immune system, bringing about the question why bone needs a cell regulated by the immune system to remove the extracellular matrix components. Recently, osteoclasts have been demonstrated to contribute to the hematopoietic stem cell niche, controlling local calcium concentration and regulating the turnover of factors essential for hematopoietic stem cell mobilization. Finally, osteoclasts are important regulators of osteoblast activity and angiogenesis, both by releasing factors stored in the bone matrix, and secreting "clastokines" that regulate the activity of neighboring cells. All these facets will be discussed in this review article, with the aim of underscoring The Great Beauty of the osteoclast. © 2014 Elsevier Inc. All rights reserved.


Ferreira A.,University of Minho | Silva J.,University of Minho | Sencadas V.,University of Minho | Ribelles J.L.G.,Polytechnic University of Valencia | And 3 more authors.
Macromolecular Materials and Engineering | Year: 2010

Electroactive macroporous poly[(vinylidene fluoride)-co-trifluoroethylene] membranes have been produced by solvent evaporation at room temperature, starting with a diluted solution of the copolymer in dimethylformamide. The pore architecture consists of interconnected spherical pores. This architecture is independent of the membrane thickness. The thickness of the membranes ranges from a few to several hundred mm, using spin coating and evaporation in static conditions, respectively. The pore structure is explained by a spinodal decomposition of the liquid/liquid phase separation and crystallization in the copolymer-rich phase.© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Salmeron-Sanchez M.,Polytechnic University of Valencia | Salmeron-Sanchez M.,CIBER ISCIII | Salmeron-Sanchez M.,Regenerative Medicine Unit | Rico P.,Polytechnic University of Valencia | And 5 more authors.
Biomaterials | Year: 2011

Fibronectin (FN) is a ubiquitous extracellular matrix protein (ECM) protein that is organized into fibrillar networks by cells through an integrin-mediated process that involves contractile forces. This assembly allows for the unfolding of the FN molecule, exposing cryptic domains that are not available in the native globular FN structure and activating intracellular signalling complexes. However, organization of FN into a physiological fibrillar network upon adsorption on a material surface has not been observed. Here we demonstrate cell-free, material-induced FN fibrillogenesis into a biological matrix with enhanced cellular activities. We found that simple FN adsorption onto poly(ethyl acrylate) surfaces, but not control polymers, triggered FN organization into a fibrillar network via interactions in the amino-terminal 70 kDa fragment, which is involved in the formation of cell-mediated FN fibrils. Moreover, the material-driven FN fibrils exhibited enhanced biological activities in terms of myogenic differentiation compared to individual FN molecules and even type I collagen. Our results demonstrate that molecular assembly of FN can take place at the material interface, giving rise to a physiological protein network similar to fibrillar matrices assembled by cells. This research identifies material surfaces that trigger the organization of extracellular matrix proteins into biological active fibrils and establishes a new paradigm to engineer ECM-mimetic biomaterials. © 2010 Elsevier Ltd.

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