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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Journal Article•DOI•

Cellular and Molecular Pathways Leading to External Root Resorption.

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Alejandro Iglesias-Linares¹, James K. Hartsfield²•Institutions (2)

Complutense University of Madrid¹, University of Kentucky²

01 Feb 2017-Journal of Dental Research

TL;DR: A substantial number of in vitro and in vivo molecular, genomic, and proteomic studies have supplied data that provide new insights into root resorption and root surface repair processes.

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Abstract: External apical root resorption during orthodontic treatment implicates specific molecular pathways that orchestrate nonphysiologic cellular activation To date, a substantial number of in vitro and in vivo molecular, genomic, and proteomic studies have supplied data that provide new insights into root resorption Recent mechanisms and developments reviewed here include the role of the cellular component—specifically, the balance of CD68+, iNOS+ M1- and CD68+, CD163+ M2-like macrophages associated with root resorption and root surface repair processes linked to the expression of the M1-associated proinflammatory cytokine tumor necrosis factor, inducible nitric oxide synthase, the M1 activator interferon γ, the M2 activator interleukin 4, and M2-associated anti-inflammatory interleukin 10 and arginase I Insights into the role of mesenchymal dental pulp cells in attenuating dentin resorption in homeostasis are also reviewed Data on recently deciphered molecular pathways are reviewed at the level of (1) cl

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108 citations

Cites background from "Nano-topography sensing by osteocla..."

...Similarly, root dentin induces a sharper increase in the number of resorption pits, with 3,134 pits/cm2 in dentin, compared with 449 pits/cm2 in bone (Geblinger et al. 2010)....
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...Similarly, root dentin induces a sharper increase in the number of resorption pits, with 3,134 pits/cm(2) in dentin, compared with 449 pits/cm(2) in bone (Geblinger et al. 2010)....
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Journal Article•DOI•

Multifunctional role of osteopontin in directing intrafibrillar mineralization of collagen and activation of osteoclasts.

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Douglas E. Rodriguez¹, Taili Thula-Mata¹, Edgardo J. Toro¹, Ya-Wen Yeh¹, Carl Holt², L. Shannon Holliday¹, Laurie B. Gower¹ - Show less +3 more•Institutions (2)

University of Florida¹, University of Glasgow²

01 Jan 2014-Acta Biomaterialia

TL;DR: It is shown that osteopontin (OPN) can similarly serve as a process-directing agent for the intrafibrillar mineralization of collagen, even though OPN is generally considered a mineralization inhibitor.

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103 citations

Journal Article•DOI•

Podosomes in adhesion, migration, mechanosensing and matrix remodeling

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Hannah Schachtner¹, Simon Calaminus², Steven G. Thomas³, Laura M. Machesky¹•Institutions (3)

University of Glasgow¹, Hull York Medical School², University of Birmingham³

01 Oct 2013-Cytoskeleton

TL;DR: The structure and composition of podosomes and also their functions in various cell types of both myeloid and endothelial lineage are reviewed and the emerging idea that podosome can sense matrix stiffness and enable cells to respond to their environment is discussed.

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Abstract: Cells use various actin-based motile structures to allow them to move across and through matrix of varying density and composition. Podosomes are actin cytoskeletal structures that form in motile cells and that mediate adhesion to substrate, migration, and other specialized functions such as transmigration through cell and matrix barriers. The podosome is a unique and interesting entity, which appears in the light microscope as an individual punctum, but is linked to other podosomes like a node on a network of the underlying cytoskeleton. Here, we discuss the signals that control podosome assembly and dynamics in different cell types and the actin organising proteins that regulate both the inner actin core and integrin-rich surrounding ring structures. We review the structure and composition of podosomes and also their functions in various cell types of both myeloid and endothelial lineage. We also discuss the emerging idea that podosomes can sense matrix stiffness and enable cells to respond to their environment.

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99 citations

Cites result from "Nano-topography sensing by osteocla..."

...This resulted in the formation of small unstable sealing zones (lifetime 8 min) in contrast to large and stable (lifetime 6 h) actin rings on a rough substrate [Geblinger et al., 2010]....
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Journal Article•DOI•

Degradation, Bioactivity, and Osteogenic Potential of Composites Made of PLGA and Two Different Sol–Gel Bioactive Glasses

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Elżbieta Pamuła¹, J. Kokoszka¹, Katarzyna Cholewa-Kowalska¹, Maria Laczka¹, Lukasz Kantor¹, Lukasz Niedzwiedzki², Gwendolen C. Reilly³, Joanna Filipowska², Wojciech Madej², Malgorzata Kolodziejczyk², Grzegorz Tylko², Anna M. Osyczka² - Show less +8 more•Institutions (3)

AGH University of Science and Technology¹, Jagiellonian University², University of Sheffield³

13 Apr 2011-Annals of Biomedical Engineering

TL;DR: In this article, the authors developed poly(l-lactide-co-glycolide) (PLGA) based composites using sol-gel derived bioactive glasses (S-BG), previously described by their group, as composite components.

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Abstract: We have developed poly(l-lactide-co-glycolide) (PLGA) based composites using sol–gel derived bioactive glasses (S-BG), previously described by our group, as composite components. Two different composite types were manufactured that contained either S2—high content silica S-BG, or A2—high content lime S-BG. The composites were evaluated in the form of sheets and 3D scaffolds. Sheets containing 12, 21, and 33 vol.% of each bioactive glass were characterized for mechanical properties, wettability, hydrolytic degradation, and surface bioactivity. Sheets containing A2 S-BG rapidly formed a hydroxyapatite surface layer after incubation in simulated body fluid. The incorporation of either S-BG increased the tensile strength and Young’s modulus of the composites and tailored their degradation rates compared to starting compounds. Sheets and 3D scaffolds were evaluated for their ability to support growth of human bone marrow cells (BMC) and MG-63 cells, respectively. Cells were grown in non-differentiating, osteogenic or osteoclast-inducing conditions. Osteogenesis was induced with either recombinant human BMP-2 or dexamethasone, and osteoclast formation with M-CSF. BMC viability was lower at higher S-BG content, though specific ALP/cell was significantly higher on PLGA/A2-33 composites. Composites containing S2 S-BG enhanced calcification of extracellular matrix by BMC, whereas incorporation of A2 S-BG in the composites promoted osteoclast formation from BMC. MG-63 osteoblast-like cells seeded in porous scaffolds containing S2 maintained viability and secreted collagen and calcium throughout the scaffolds. Overall, the presented data show functional versatility of the composites studied and indicate their potential to design a wide variety of implant materials differing in physico-chemical properties and biological applications. We propose these sol–gel derived bioactive glass–PLGA composites may prove excellent potential orthopedic and dental biomaterials supporting bone formation and remodeling.

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79 citations

Journal Article•DOI•

Integrin diversity brings specificity in mechanotransduction.

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Shailaja Seetharaman¹, Shailaja Seetharaman², Sandrine Etienne-Manneville²•Institutions (2)

Paris Descartes University¹, Pasteur Institute²

01 Mar 2018-Biology of the Cell

TL;DR: How the expression of particular integrin subtypes affects cellular adaptation to substrate rigidity is described and the role of integrins and associated proteins in mechanotransduction is explained, focusing on their specificity in mechanosensing and force transmission.

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77 citations

Cites background from "Nano-topography sensing by osteocla..."

...Despite this, podosomes in osteoclasts have been shown to respond to ECM properties such as rigidity and texture [Geblinger et al., 2010]....
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Journal Article•DOI•

Matrix elasticity directs stem cell lineage specification.

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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)....
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...…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)....
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...…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)....
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...…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)....
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Journal Article•DOI•

Tissue Cells Feel and Respond to the Stiffness of Their Substrate

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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…...
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...…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)....
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Journal Article•DOI•

Geometric control of cell life and death.

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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.

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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)....
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...…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…...
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Journal Article•DOI•

Cell Movement Is Guided by the Rigidity of the Substrate

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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)....
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Journal Article•DOI•

Taking Cell-Matrix Adhesions to the Third Dimension

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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)....
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...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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