Nano-topography sensing by osteoclasts.

doi:10.1242/JCS.060954

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Nano-topography sensing by osteoclasts.

Journal Article•DOI•

Nano-topography sensing by osteoclasts.

Dafna Geblinger¹, Lia Addadi¹, Benjamin Geiger¹•Institutions (1)

Weizmann Institute of Science¹

01 May 2010-Journal of Cell Science (The Company of Biologists Ltd)-Vol. 123, Iss: 10, pp 1503-1510

TL;DR: It was observed that steps or sub-micrometer cracks on the smooth surface stimulate local ring formation, raising the possibility that similar imperfections on bone surfaces may stimulate local osteoclast resorptive activity.

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Abstract: Bone resorption by osteoclasts depends on the assembly of a specialized, actin-rich adhesive ‘sealing zone’ that delimits the area designed for degradation. In this study, we show that the level of roughness of the underlying adhesive surface has a profound effect on the formation and stability of the sealing zone and the associated F-actin. As our primary model substrate, we use ‘smooth’ and ‘rough’ calcite crystals with average topography values of 12 nm and 530 nm, respectively. We show that the smooth surfaces induce the formation of small and unstable actin rings with a typical lifespan of ~8 minutes, whereas the sealing zones formed on the rough calcite surfaces are considerably larger, and remain stable for more than 6 hours. It was further observed that steps or sub-micrometer cracks on the smooth surface stimulate local ring formation, raising the possibility that similar imperfections on bone surfaces may stimulate local osteoclast resorptive activity. The mechanisms whereby the physical properties of the substrate influence osteoclast behavior and their involvement in osteoclast function are discussed.

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Dissertation•

Identification of novel factors involved in the exacerbation of HIV-1 infection and spread among macrophages in the tuberculosis context

[...]

Maeva Dupont

06 Dec 2019

TL;DR: Une analyse transcriptomique des M(cmMTB) a ete realisee, revelant deux facteurs essentiels : le recepteur Siglec-1 et les interferons de type I (IFN-I) via STAT1.

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Abstract: Mycobacterium tuberculosis (Mtb), la bacterie responsable de la tuberculose (TB), et le virus de l'immunodeficience humaine (VIH-1), l'agent du syndrome de l'immunodeficience acquise (SIDA), accelerent leurs progressions mutuelles chez les patients co-infectes. Alors que de nombreuses donnees cliniques rapportent une augmentation de la charge virale dans les sites anatomiques co-infectes, les mecanismes qui en sont responsables restent insuffisamment decrits. Mtb cible principalement les macrophages. Nous emettons l'hypothese que l'infection des macrophages par Mtb cree un microenvironnement propice a la replication du VIH-1 au niveau des sites co-infectes. Pour le montrer, j'ai utilise un modele in vitro precedemment etabli par mes equipes (le cmMTB - pour " conditioned media of Mtb-infected macrophages "). Celui-ci permet de mimer un environnement tuberculeux, par la differenciation et l'activation des macrophages vers un profil " M(cmMTB) ", largement retrouve dans les poumons lors d'une tuberculose active. En rejoignant le laboratoire, j'ai participe a l'etude des mecanismes responsables de l'augmentation de la replication virale dans le contexte de co-infection, en utilisant ce modele. Nous avons trouve que les M(cmMTB) forment de nombreux nanotubes (ponts intercellulaires), leur permettant de transferer plus de virus d'un macrophage a l'autre, et conduit a une forte augmentation de la production virale. L'objectif principal de ma these a donc ete d'identifier, dans un contexte tuberculeux, de nouveaux facteurs impliques dans l'augmentation de la replication du VIH-1 dans les macrophages. Pour cela, une analyse transcriptomique des M(cmMTB) a ete realisee, revelant deux facteurs essentiels : le recepteur Siglec-1 et les interferons de type I (IFN-I) via STAT1. Dans un premier temps, j'ai etudie le role de Siglec-1 dans la synergie entre Mtb et le VIH-1 dans les macrophages. D'abord, j'ai montre que son expression de surface etait augmentee par le cmMTB, de facon dependante des IFN-I. Ensuite, j'ai etabli que l'abondance des macrophages alveolaires exprimant Siglec-1 chez les primates non-humains co-infectes avec Mtb et le virus de l'immunodeficience simienne correlait avec la severite de la pathologie, et etait associee a la signalisation des IFN-I, via l'activation de STAT1. De plus, j'ai identifie une nouvelle localisation de Siglec-1 le long d'un sous-type de nanotubes. Ceux-ci, plus larges et plus longs, contenaient plus de VIH-1 que les autres, suggerant que le virus puisse les emprunter en majorite. Enfin, j'ai montre que Siglec-1 etait responsable de l'augmentation de la replication du VIH-1, grâce a une meilleure capture du virus et de son transfert intercellulaire, potentiellement grâce aux nanotubes. Ces resultats permettent de proposer que Siglec-1 a un role physiologique dans la biologie des nanotubes et des macrophages. Dans un second temps, j'ai determine que la TB deregule la signalisation IFN-I/STAT1 dans les macrophages et diminue leur reponse antivirale. Apres stimulation des M(cmMTB) par de l'IFN-I exogene, j'ai demontre une diminution de l'activation de STAT1 et de l'expression des genes de reponse a l'IFN, indiquant une potentielle desensibilisation de ces cellules a l'IFN-I. Ces observations, ainsi que la perte de controle de la replication du VIH-1, ont ete reversees par l'inhibition du recepteur aux IFN-I (IFNAR2) ou du facteur de transcription STAT1. Ensemble, ces resultats indiquent que les IFN-I ont un role deletere pour l'hote dans le contexte de la co-infection. Mon projet de these a permis de reveler la capacite de Mtb a dereguler les reponses antivirales de l'hote contre le VIH-1, participant ainsi a la gravite de la co-infection. Les facteurs identifies au cours de ma these pourraient a plus long terme etre utilises a des fins diagnostiques ou therapeutiques, dans le but d'ameliorer la prise en charge des patients co-infectes.

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2 citations

Book Chapter•DOI•

Actin Organizing Proteins in Regulation of Osteoclast Function

[...]

Brooke K. McMichael¹, Beth S. Lee¹•Institutions (1)

Ohio State University¹

01 Jan 2015

TL;DR: This chapter summarizes the current understanding of osteoclast cytoskeletal dynamics with particular emphasis on actin binding proteins that organize the cytoskeleton to facilitate the differentiation and function of these distinctive cells.

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Abstract: As products of cell–cell fusion and as highly mobile, bone-degrading cells, osteoclasts require a unique, abundantly adaptable actin cytoskeleton. This chapter summarizes the current understanding of osteoclast cytoskeletal dynamics with particular emphasis on actin binding proteins that organize the cytoskeleton to facilitate the differentiation and function of these distinctive cells.

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2 citations

Dissertation•

Mechanics and Dynamics of Cell Adhesion : Experimental Study of the Osteoclasts

[...]

Shiqiong Hu¹•Institutions (1)

École normale supérieure de Lyon¹

01 Jan 2010

TL;DR: Analysis of osteoclast migration, and the forces it applies on the substrate, demonstrates that the internal dynamics of the actin within the cell does not only correlate with cell migration, but drives it.

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Abstract: Osteoclasts are large, multinucleated cells, which resorb mineralized bone When an osteoclast encounters a substrate, dot-like actin-rich structures, the podosomes, appear and assemble into clusters, rings or a belt We experimentally investigate, from a cell population to a single podosome, their function and dynamics Over a cell population, kinetic measurements show that the cell surface area A scales as A ~ K2, where K is the number of nuclei, indicating a flat morphology By defining quantities that account for the spatial distribution of the actin within the cell, we demonstrate that the podosomes organization only depends on the time after differentiation, and not on K In a single osteoclast, the observation of a strong coupling between cell spreading and podosomes formation lead us to propose that podosomes play an important role in osteoclast motility Analysis of osteoclast migration, and the forces it applies on the substrate, demonstrates that the internal dynamics of the actin within the cell does not only correlate with cell migration, but drives it Finally, in order to understand the internal dynamics of a single podosome, we improved the model of Biben et al (2005) by considering on the one hand, actin polymerization, and on the other hand, diffusion and attachment kinetics of the gelsolin, an actin severing protein We find that podosomes are mainly governed by the actin dynamics, regardless of gelsolin concentration

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2 citations

Book Chapter•DOI•

Propagation of Human Bone Marrow Stem Cells for Craniofacial Applications

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A. Pelaez-Vargas¹, Daniel Gallego-Perez², David F. Gomez³, Maria Helena Fernandes¹, Derek J. Hansford², Fernando J. Monteiro¹ - Show less +2 more•Institutions (3)

University of Porto¹, Ohio State University², University of Antioquia³

01 Jan 2012

TL;DR: This chapter is mainly focused on the collection and ex-vivo propagation of hBMSCs/osteoprogenitors and their behavior in engineered microenvironments for craniofacial applications.

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Abstract: Cleft lip and/or palate is the second most frequent congenital defect in humans. Patients with this defect are treated by multi-disciplinary teams, which provide corrective procedures to improve aesthetic and function, as well as permanent psychosocial support. Frequently, these patients have corrective surgical procedures conducted to repair bone defects using different bone sources. Generally, modern surgical results are successful, although they can be improved in some aspects such as their reliability, especially for growing children. Novel combined approaches based on tissue engineering and Mesenchymal Stem Cells (MSCs) have been proposed. This chapter is mainly focused on the collection and ex-vivo propagation of hBMSCs/osteoprogenitors and their behavior in engineered microenvironments for craniofacial applications. Different aspects of isolation, propagation and osteoblastic phenotype expression are described. Also, the microfabrication of microenvironments and their effects on molecular and cellular components are explained.

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2 citations

Book Chapter•DOI•

Engineered ECM Microenvironments and Their Regulation of Stem Cells

[...]

Yu Suk Choi¹, Andrew W. Holle¹, Adam J. Engler¹•Institutions (1)

University of California, San Diego¹

01 Jan 2013

TL;DR: The recent advances in nano- or microfabrication techniques, the biomechanical- and biophysical-driven stem cell differentiation, and the mechanism of how cells “feel” their ECM environment are detailed.

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Abstract: Stem cells possess numerous therapeutic benefits since it is possible to reproducibly control their ability to mature into different cell types even after prolonged culture in vitro; this ability makes stem cells well suited for tissue engineering and regenerative applications. Consequently, understanding stem cell differentiation is a crucial step for those applications. Regulating stem cell fate has traditionally relied on presenting small molecules such as growth factors and cytokines in developmentally appropriate ways, but such a view overlooks other important niche characteristics. Recently, extracellular matrix (ECM) properties have been shown to influence cellular behavior independent of chemical signals, and this has shifted the differentiation paradigm to include ECM properties, e.g. topography, stiffness, composition, porosity, and cell shape/size. Recent advances in bioengineering have enabled versatility in patterning cell types with controlled chemistries, geometries, and sizes. In this chapter, we detail the recent advances in nano- or microfabrication techniques, the biomechanical- and biophysical-driven stem cell differentiation, and the mechanism of how cells “feel” their ECM environment.

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2 citations

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References

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Journal Article•DOI•

Matrix elasticity directs stem cell lineage specification.

[...]

Adam J. Engler¹, Shamik Sen¹, H. Lee Sweeney¹, Dennis E. Discher•Institutions (1)

University of Pennsylvania¹

25 Aug 2006-Cell

TL;DR: Naive mesenchymal stem cells are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types.

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12,204 citations

"Nano-topography sensing by osteocla..." refers background in this paper

...…cell proliferation, gene expression and cell viability (Bershadsky et al., 2006a; Chen et al., 1997; Diener et al., 2005; Discher et al., 2005; Engler et al., 2006; Geiger et al., 2009; Kunzler et al., 2007; Lo et al., 2000; Roach et al., 2007; Saltel et al., 2004; Vogel and Sheetz, 2006)....
[...]
...…et al., 1999; Roach et al., 2007; Shimizu et al., 1989), local density of the adhesive ligands (Arnold et al., 2004; Arnold et al., 2008; Hirschfeld-Warneken et al., 2008), and physical properties (Bershadsky et al., 2006a; Bershadsky et al., 2006b; Engler et al., 2006; Vogel and Sheetz, 2006)....
[...]
...…a widespread cellular phenomenon, whereby cells collect information on the substrate on which they grow, integrate it, and develop a response (Bershadsky et al., 2006a; Chen et al., 1997; Diener et al., 2005; Discher et al., 2005; Engler et al., 2006; Geiger et al., 2009; Vogel and Sheetz, 2006)....
[...]
...…respond to chemical and physical properties of the underlying matrix, such as rigidity, mechanical activity, ligand density and dimensionality (Bershadsky et al., 2006a; Chen et al., 1997; Diener et al., 2005; Discher et al., 2005; Engler et al., 2006; Geiger et al., 2009; Vogel and Sheetz, 2006)....
[...]

Journal Article•DOI•

Tissue Cells Feel and Respond to the Stiffness of Their Substrate

[...]

Dennis E. Discher¹, Paul A. Janmey¹, Yu-li Wang²•Institutions (2)

University of Pennsylvania¹, University of Massachusetts Medical School²

18 Nov 2005-Science

TL;DR: An understanding of how tissue cells—including fibroblasts, myocytes, neurons, and other cell types—sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels with which elasticity can be tuned to approximate that of tissues.

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Abstract: Normal tissue cells are generally not viable when suspended in a fluid and are therefore said to be anchorage dependent. Such cells must adhere to a solid, but a solid can be as rigid as glass or softer than a baby's skin. The behavior of some cells on soft materials is characteristic of important phenotypes; for example, cell growth on soft agar gels is used to identify cancer cells. However, an understanding of how tissue cells-including fibroblasts, myocytes, neurons, and other cell types-sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels (or to other cells) with which elasticity can be tuned to approximate that of tissues. Key roles in molecular pathways are played by adhesion complexes and the actinmyosin cytoskeleton, whose contractile forces are transmitted through transcellular structures. The feedback of local matrix stiffness on cell state likely has important implications for development, differentiation, disease, and regeneration.

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5,889 citations

"Nano-topography sensing by osteocla..." refers background in this paper

...…a widespread cellular phenomenon, whereby cells collect information on the substrate on which they grow, integrate it, and develop a response (Bershadsky et al., 2006a; Chen et al., 1997; Diener et al., 2005; Discher et al., 2005; Engler et al., 2006; Geiger et al., 2009; Vogel and Sheetz, 2006)....
[...]
...…migration, ECM remodeling, cell proliferation, gene expression and cell viability (Bershadsky et al., 2006a; Chen et al., 1997; Diener et al., 2005; Discher et al., 2005; Engler et al., 2006; Geiger et al., 2009; Kunzler et al., 2007; Lo et al., 2000; Roach et al., 2007; Saltel et al., 2004; Vogel…...
[...]
...…respond to chemical and physical properties of the underlying matrix, such as rigidity, mechanical activity, ligand density and dimensionality (Bershadsky et al., 2006a; Chen et al., 1997; Diener et al., 2005; Discher et al., 2005; Engler et al., 2006; Geiger et al., 2009; Vogel and Sheetz, 2006)....
[...]

Journal Article•DOI•

Geometric control of cell life and death.

[...]

Christopher S. Chen¹, Milan Mrksich¹, Sui Huang¹, George M. Whitesides¹, Donald E. Ingber¹ - Show less +1 more•Institutions (1)

Harvard University¹

30 May 1997-Science

TL;DR: Human and bovine capillary endothelial cells were switched from growth to apoptosis by using micropatterned substrates that contained extracellular matrix-coated adhesive islands of decreasing size to progressively restrict cell extension.

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Abstract: Human and bovine capillary endothelial cells were switched from growth to apoptosis by using micropatterned substrates that contained extracellular matrix-coated adhesive islands of decreasing size to progressively restrict cell extension. Cell spreading also was varied while maintaining the total cell-matrix contact area constant by changing the spacing between multiple focal adhesion-sized islands. Cell shape was found to govern whether individual cells grow or die, regardless of the type of matrix protein or antibody to integrin used to mediate adhesion. Local geometric control of cell growth and viability may therefore represent a fundamental mechanism for developmental regulation within the tissue microenvironment.

...read moreread less

4,641 citations

"Nano-topography sensing by osteocla..." refers background in this paper

...…a widespread cellular phenomenon, whereby cells collect information on the substrate on which they grow, integrate it, and develop a response (Bershadsky et al., 2006a; Chen et al., 1997; Diener et al., 2005; Discher et al., 2005; Engler et al., 2006; Geiger et al., 2009; Vogel and Sheetz, 2006)....
[...]
...…respond to chemical and physical properties of the underlying matrix, such as rigidity, mechanical activity, ligand density and dimensionality (Bershadsky et al., 2006a; Chen et al., 1997; Diener et al., 2005; Discher et al., 2005; Engler et al., 2006; Geiger et al., 2009; Vogel and Sheetz, 2006)....
[...]
...…cellular processes, including adhesion, migration, ECM remodeling, cell proliferation, gene expression and cell viability (Bershadsky et al., 2006a; Chen et al., 1997; Diener et al., 2005; Discher et al., 2005; Engler et al., 2006; Geiger et al., 2009; Kunzler et al., 2007; Lo et al., 2000; Roach…...
[...]

Journal Article•DOI•

Cell Movement Is Guided by the Rigidity of the Substrate

[...]

Chun Min Lo¹, Hong Bei Wang¹, Micah Dembo², Yu-li Wang¹•Institutions (2)

University of Massachusetts Medical School¹, Boston University²

01 Jul 2000-Biophysical Journal

TL;DR: It is discovered that changes in tissue rigidity and strain could play an important controlling role in a number of normal and pathological processes involving cell locomotion, including morphogenesis, the immune response, and wound healing.

...read moreread less

3,189 citations

"Nano-topography sensing by osteocla..." refers background in this paper

...…cell proliferation, gene expression and cell viability (Bershadsky et al., 2006a; Chen et al., 1997; Diener et al., 2005; Discher et al., 2005; Engler et al., 2006; Geiger et al., 2009; Kunzler et al., 2007; Lo et al., 2000; Roach et al., 2007; Saltel et al., 2004; Vogel and Sheetz, 2006)....
[...]

Journal Article•DOI•

Taking Cell-Matrix Adhesions to the Third Dimension

[...]

Edna Cukierman¹, Roumen Pankov¹, Daron R. Stevens¹, Kenneth M. Yamada¹•Institutions (1)

National Institutes of Health¹

23 Nov 2001-Science

TL;DR: These distinctive in vivo 3D-matrix adhesions differ in structure, localization, and function from classically described in vitro adhesion, and as such they may be more biologically relevant to living organisms.

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Abstract: Adhesions between fibroblastic cells and extracellular matrix have been studied extensively in vitro, but little is known about their in vivo counterparts. Here, we characterized the composition and function of adhesions in three-dimensional (3D) matrices derived from tissues or cell culture. "3D-matrix adhesions" differ from focal and fibrillar adhesions characterized on 2D substrates in their content of alpha5beta1 and alphavbeta3 integrins, paxillin, other cytoskeletal components, and tyrosine phosphorylation of focal adhesion kinase (FAK). Relative to 2D substrates, 3D-matrix interactions also display enhanced cell biological activities and narrowed integrin usage. These distinctive in vivo 3D-matrix adhesions differ in structure, localization, and function from classically described in vitro adhesions, and as such they may be more biologically relevant to living organisms.

...read moreread less

3,000 citations

"Nano-topography sensing by osteocla..." refers background in this paper

...Many cell types react to changes in the threedimensional texture of the substrate at the nanometer- and micrometer scales, by altering their adhesion, motility and orientation (Cukierman et al., 2001; Curtis and Wilkinson, 1997; Geiger, 2001; Vogel and Sheetz, 2006)....
[...]
...The interplay between topography, force and adhesion dynamics might also affect other, mechanosensitive adhesions such as focal adhesions, possibly accounting for changes in their stability, signaling activity and dynamics, when plated on a rough threedimensional matrix (Cukierman et al., 2001)....
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