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•

Balancing forces: architectural control of mechanotransduction

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Christopher C. DuFort¹, Matthew J. Paszek¹, Valerie M. Weaver¹•Institutions (1)

University of California, San Francisco¹

01 May 2011-Nature Reviews Molecular Cell Biology

TL;DR: Sustained disruptions in tensional homeostasis can be caused by alterations in the extracellular matrix, allowing it to serve as a mechanically based memory-storage device that can perpetuate a disease or restore normal tissue behaviour.

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Abstract: All cells exist within the context of a three-dimensional microenvironment in which they are exposed to mechanical and physical cues. These cues can be disrupted through perturbations to mechanotransduction, from the nanoscale-level to the tissue-level, which compromises tensional homeostasis to promote pathologies such as cardiovascular disease and cancer. The mechanisms of such perturbations suggest that a complex interplay exists between the extracellular microenvironment and cellular function. Furthermore, sustained disruptions in tensional homeostasis can be caused by alterations in the extracellular matrix, allowing it to serve as a mechanically based memory-storage device that can perpetuate a disease or restore normal tissue behaviour.

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875 citations

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

...On a more specific level, the spatial presentation of ECM ligands, such as fibronectin, vitronectin, laminin and collagen, and the nanotopography of the ECM, control integrin organization, adhesion assembly, and signal transduction to direct cell behaviou...
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Journal Article•DOI•

Molecular Architecture and Function of Matrix Adhesions

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Benjamin Geiger¹, Kenneth M. Yamada²•Institutions (2)

Weizmann Institute of Science¹, National Institutes of Health²

01 May 2011-Cold Spring Harbor Perspectives in Biology

TL;DR: These cell adhesions play crucial roles in cell migration, proliferation, and determination of cell fate, and are mediated by membrane receptors such as the integrins, as well as many other components that comprise the adhesome.

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Abstract: Cell adhesions mediate important bidirectional interactions between cells and the extracellular matrix. They provide an interactive interface between the extracellular chemical and physical environment and the cellular scaffolding and signaling machinery. This dynamic, reciprocal regulation of intracellular processes and the matrix is mediated by membrane receptors such as the integrins, as well as many other components that comprise the adhesome. Adhesome constituents assemble themselves into different types of cell adhesion structures that vary in molecular complexity and change over time. These cell adhesions play crucial roles in cell migration, proliferation, and determination of cell fate.

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507 citations

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

...Cells can also respond to the micro- or even nano-topography of a surface to which they adhere (Curtis and Wilkinson 1997; Cukierman et al. 2001; Geiger et al. 2001; Baharloo et al. 2005; Grossner-Schreiber et al. 2006; Vogel et al. 2006; Geblinger et al. 2010)....
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...They can assemble into large, belt-like superstructures, and are implicated in matrix-modulating activities (e.g., bone resorption by osteoclasts (Geblinger et al. 2010) and matrix invasion by a variety of cancer cells (Gimona et al. 2008)....
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...2006), regulating their dynamic properties (Geblinger et al. 2010), and modulating their signaling activity....
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...Cells can also respond to the micro-topography or even nano-topography of a surface to which they adhere (Curtis and Wilkinson 1997; Cukierman et al. 2001; Geiger et al. 2001; Baharloo et al. 2005; Grossner-Schreiber et al. 2006; Vogel et al. 2006; Geblinger et al. 2010)....
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...…surface features that are known to play a role in guiding the formation of matrix adhesions (Cukierman et al. 2001; Geiger et al. 2001; Baharloo et al. 2005; Grossner-Schreiber et al. 2006), regulating their dynamic properties (Geblinger et al. 2010) and modulating their signaling activity....
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Journal Article•DOI•

Nanotopographical Control of Stem Cell Differentiation

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Laura E. McNamara¹, Rebecca J. McMurray¹, Manus J.P. Biggs², Fahsai Kantawong¹, Richard O.C. Oreffo³, Matthew J. Dalby¹ - Show less +2 more•Institutions (3)

University of Glasgow¹, Columbia University², University of Southampton³

01 Jan 2010-Journal of Tissue Engineering

TL;DR: Nanotopography is examined as a means to guide differentiation, and its application is described in the context of different subsets of stem cells, with a particular focus on skeletal (mesenchymal) stem cells.

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Abstract: Stem cells have the capacity to differentiate into various lineages, and the ability to reliably direct stem cell fate determination would have tremendous potential for basic research and clinical therapy. Nanotopography provides a useful tool for guiding differentiation, as the features are more durable than surface chemistry and can be modified in size and shape to suit the desired application. In this paper, nanotopography is examined as a means to guide differentiation, and its application is described in the context of different subsets of stem cells, with a particular focus on skeletal (mesenchymal) stem cells. To address the mechanistic basis underlying the topographical effects on stem cells, the likely contributions of indirect (biochemical signal-mediated) and direct (force-mediated) mechanotransduction are discussed. Data from proteomic research is also outlined in relation to topography-mediated fate determination, as this approach provides insight into the global molecular changes at the level of the functional effectors.

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349 citations

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

...diverse cell types including fibroblasts [18, 22], osteoblasts [23], osteoclasts [24, 25], endothelial [15], smooth muscle [26], epithelial [27, 28], and epitenon cells [16]....
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Journal Article•DOI•

Degrading devices: invadosomes in proteolytic cell invasion.

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Stefan Linder, Christiane Wiesner, Mirko Himmel

10 Oct 2011-Annual Review of Cell and Developmental Biology

TL;DR: An overview of the field is provided, with special focus on current developments such as intracellular transport processes, ultrastructural analysis, the possible involvement of invadosomes in disease, and the tentative identification of invadoomes in 3D environments and in vivo.

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Abstract: Podosomes and invadopodia, collectively known as invadosomes, are cell-matrix contacts in a variety of cell types, such as monocytic cells or cancer cells, that have to cross tissue barriers. Both structures share an actin-rich core, which distinguishes them from other matrix contacts, and are regulated by a multitude of signaling pathways including RhoGTPases, kinases, actin-associated proteins, and microtubule-dependent transport. Invadosomes recruit and secrete proteinases and are thus able to lyse extracellular matrix components. They are therefore considered to be potential key structures in proteolytic cell invasion in both physiological and pathological settings. This review provides an overview of the field, with special focus on current developments such as intracellular transport processes, ultrastructural analysis, the possible involvement of invadosomes in disease, and the tentative identification of invadosomes in 3D environments and in vivo.

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346 citations

Journal Article•DOI•

Extracellular matrix networks in bone remodeling.

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Andrea I. Alford¹, Kenneth M. Kozloff¹, Kurt D. Hankenson²•Institutions (2)

University of Michigan¹, Michigan State University²

01 Aug 2015-The International Journal of Biochemistry & Cell Biology

TL;DR: This comprehensive review will focus on how networks of ECM proteins function to regulate osteoclast- and osteoblast-mediated bone remodeling and the clinical significance of these networks on normal bone and as they relate to pathologies of bone mass and geometry will be considered.

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223 citations

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Journal Article•DOI•

Titanium surface roughness accelerates RANKL-dependent differentiation in the osteoclast precursor cell line, RAW264.7.

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Seicho Makihira¹, Yuichi Mine¹, Eduardo Kosaka¹, Hiroki Nikawa¹•Institutions (1)

Hiroshima University¹

01 Sep 2007-Dental Materials Journal

TL;DR: It is suggested that titanium surface roughness facilitated osteoclast differentiation through the activation of the RANK-TRAF6 signaling network.

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Abstract: The present study was a molecular analysis of the initial differentiation of osteoclast precursor RAW264.7 cells on titanium specimens. RAW264.7 cell line was cultured on titanium specimens of which the surfaces were finished by wet grinding with 2000-, 1200-, 600-, or 180-grit waterproof abrasive paper. Total RNA was extracted from cells cultured in the presence or absence of Receptor Activator of NF-kappaB Ligand (RANKL), prior to cDNA synthesis for real-time quantitative reverse transcriptase-polymerase chain reaction analysis. Titanium surfaces initially enhanced the expression of osteoclast differentiation markers including tartrate-resistant acid phosphatase and cathepsin K in RAW264.7 cells cultured with RANKL stimulation, in a roughness-dependent manner. The mRNA expressions of both RANKL receptor, RANK, and its adapter protein TNF receptor-associated factor 6 (TRAF6) increased when RAW264.7 cells were cultured on titanium specimens with roughened surfaces, as compared with that of control specimen with a polished surface. These results, taken together, suggested that titanium surface roughness facilitated osteoclast differentiation through the activation of the RANK-TRAF6 signaling network.

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55 citations

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

...Osteoclast resorptive activity on ceramic substrates was shown to be enhanced by introducing nanometerscale roughness (Webster, 2001), and osteoclast differentiation was shown to be enhanced on rough metallic implant surfaces (Makihira et al., 2007; Marchisio et al., 2005)....
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Journal Article•DOI•

Implant surface roughness influences osteoclast proliferation and differentiation.

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Marco Marchisio¹, Maristella Di Carmine¹, Rita Pagone¹, Adriano Piattelli¹, Sebastiano Miscia¹ - Show less +1 more•Institutions (1)

University of Chieti-Pescara¹

01 Nov 2005-Journal of Biomedical Materials Research Part B

TL;DR: Results could explain the higher bone-implant contact percentage found around implants with rougher surfaces and suggest that osteoclasts may play an important role in the initial period after implant placement to prime or prepare the implant surface for the osteoblast activity.

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Abstract: The osteoclast is a hematopoietic cell derived from CFU-GM and branches from the monocyte-macrophage lineage during the differentiation process. Biological environment appears to be crucial for osteoclast formation and activity. It has been reported that bone remodeling following implant placement requires a coordinated activity by osteoclasts and osteoblasts. The response of such cells at the bone-implant interface has been suggested to be affected by the structural and morphological features of the biomaterial surface. To shed more light on this topic we performed a multiparametric analysis of murine monocytes response to different titanium surfaces. These cells, RAW 264.7 type TIB-71, represent a very useful system because they differentiate into osteoclasts following treatment of definite doses of the osteoclast-differentiation factor RANKL and macrophage colony-stimulating factor (M-CSF). Cells, cultured on glass (control), on grade 3 machined and on titanium pull-spray superficial-TPSS surfaces disclosed profound different responses in terms of morphological rearrangements, adhesion, and differentiation abilities. Indeed, after 14 days, cells cultured on glass and machined surfaces were uniformly distributed, while, on the TPSS surface cells strictly aggregated into small isolated clusters were observed. In addition, cells cultured on the machined surface displayed a higher adhesion ability, while cells cultured on the rougher surface disclosed a more evident capability to differentiate. These results could explain the higher bone-implant contact percentage found around implants with rougher surfaces and suggest that osteoclasts may play an important role in the initial period after implant placement to prime or prepare the implant surface for the osteoblast activity.

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49 citations

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

...Osteoclast resorptive activity on ceramic substrates was shown to be enhanced by introducing nanometerscale roughness (Webster, 2001), and osteoclast differentiation was shown to be enhanced on rough metallic implant surfaces (Makihira et al., 2007; Marchisio et al., 2005)....
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Journal Article•DOI•

The effect of substrate composition and condition on resorption by isolated osteoclasts

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Hideo Shimizu¹, Seizaburo Sakamoto¹, Masako Sakamoto¹, D.D. Lee¹•Institutions (1)

Harvard University¹

01 Jul 1989-Bone and Mineral

TL;DR: The difference observed between resorption of those areas of bone surface and the failure of osteoclasts to resorb non-tissue substrates are discussed in relation to current theories of the mechanisms of mineral dissolution and resorbing in mammalian calcified tissues.

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47 citations

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

...…features that can be sensed by cells are surface chemistry (Leeuwenburgh et al., 2001; Monchau et al., 2002; Redey 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…...
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Journal Article•DOI•

Surface-Induced Regulation of Podosome Organization and Dynamics in Cultured Osteoclasts

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

Weizmann Institute of Science¹

05 Jan 2009-ChemBioChem

TL;DR: It is concluded that osteoclasts sense the local properties of the underlying substrate and respond to these signals, both locally and globally.

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Abstract: Bone is continuously repaired and remodeled through the well-coordinated activity of osteoblasts, which form new bone, and osteoclasts, which resorb it. How osteoclasts sense the properties of the bone surface remains unclear. Combining light and electron microscopy, we compared osteoclast behavior on three distinct surfaces: glass, calcite single crystals, and bone. Podosomes, the basic units of the adhesion structure, and their organization into super-structures, were found to be common to cells attached to all three substrates, while the structure of the resorption organelle, the so-called “ruffled border,” markedly differed. Moreover, the integrity, stability and dynamic behavior of the adhesion super-structures also fundamentally differed, depending on the substrate. We conclude that osteoclasts sense the local properties of the underlying substrate and respond to these signals, both locally and globally.

...read moreread less

46 citations

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

...We have previously shown that actin-containing sealing zones formed on various surfaces (e.g. glass, calcite and bone) differ in their thickness, podosometo-podosome distance, and density of actin fibers interconnecting the constituting podosomes (Geblinger et al., 2009)....
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...The basic architecture of individual podosomes, and their general tendency to interact with each other via interconnecting actin fibers and form ring-like superstructures, is an intrinsic property of osteoclasts (Geblinger et al., 2009; Luxenburg et al., 2007)....
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...Thus, on both rough and smooth glass, similar, usually incomplete actin rings were formed, extending towards the cell periphery [for a detailed comparison of osteoclast behavior on glass, calcite and bone, see Geblinger et al. (Geblinger et al., 2009)]....
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...Thus, roughness on glass surfaces increases ring stability and reduces its turnover rate, similar to roughness on calcite, whereas it does not affect the absence of ring coherence that is a fundamental characteristic of osteoclast behavior on glass (Geblinger et al., 2009)....
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...The architecture of the Jo ur na l o f C el l S ci en ce podosomes, and the manner in which they assemble into sealing zones, are similar on calcite, bone and glass (Geblinger et al., 2009; Luxenburg et al., 2007)....
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