Nano-topography sensing by osteoclasts.
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.
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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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.
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.
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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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.
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.
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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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.
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.
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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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.
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.
346 citations
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.
223 citations
References
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TL;DR: It is noted that micron scale topography may have potential for influencing osseointegration, and as the magnitude of the discontinuities on SiC, Gb, and Sp were similar, the differences in cell responses does not appear to lie with the size of the features, but whether the features showed an ordered or disordered structure.
Abstract: Increased magnitude of biomaterial surface roughness and micromachined-grooved surfaces has both been shown to stimulate osteoblast activity, but have not been compared in the same study quantitatively. A series of titanium alloy (Ti6Al4V) samples were prepared using simple machining techniques to undertake such a comparison. Samples were either grit blasted (Gb) or shot peened (Sp) to give random discontinuities, or silicon carbide ground (SiC) to produce ordered grooves. These were compared with micropolished samples (Mp). The samples were coated with a 1 mum continuous coating of hydroxyapatite to remove differences in surface chemistry. Human osteoblast-like cells were seeded onto the materials and metabolic activity, proliferation, alkaline phosphatase activity, and osteocalcin production assessed. Cell responses were highly dependent on the substrate that they were cultured on. Cells cultured on the smooth and ordered (Mp and SiC, respectively) samples had higher metabolic activity and a more elongated morphology than those cultured on the randomly structured Gb or Sp samples. Over 21 days, cell metabolic activity peaked relative to the control between 7 and 14 days on the Mp sample, and between 14 and 21 days on the Gb, Sp, and SiC samples. In common with other researchers, we note that micron scale topography may have potential for influencing osseointegration. More importantly, as the magnitude of the discontinuities on SiC, Gb, and Sp were similar, the differences in cell responses does not appear to lie with the size of the features, but whether the features showed an ordered or disordered structure.
77 citations
"Nano-topography sensing by osteocla..." refers background in this paper
...Key words: Osteoclast, Bone remodeling, Cytoskeleton, Biodegradable materials, Cell adhesion Jo ur na l o f C el l S ci en ce Interestingly, the osteoblast response is affected not only by the roughness range, but also by the level of order in surface topography (Ball et al., 2008)....
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TL;DR: New findings claiming that the formation of physiological adhesions depends on the correct combination of molecular composition, topography, and pliability of the matrix are discussed.
Abstract: Cultured cells are known to form focal and fibrillar adhesions with the substrate on which they grow. But to what extent these adhesions represent those formed in vivo is a matter of debate. In a Perspective, [Geiger][1] discusses new findings ([ Cukierman et al .][2]) claiming that the formation of physiological adhesions depends on the correct combination of molecular composition, topography, and pliability of the matrix.
[1]: http://www.sciencemag.org/cgi/content/full/294/5547/1661
[2]: http://www.sciencemag.org/cgi/content/short/294/5547/1708
74 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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TL;DR: It is found that mature osteoclasts resorb more on aged than on young bone, despite unchanged adhesion and morphology, which indicates that the age of the bone plays an important role in controlling osteoclast-mediated resorption on aged bones when compared to young bones.
Abstract: We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of aged bones. Osteoclasts resorb aging bone in order to repair damage and maintain the quality of bone. The mechanism behind the targeting of aged bone for remodeling is not clear. We investigated whether bones endogenously possess the ability to control osteoclastic resorption. To biochemically distinguish aged and young bones; we measured the ratio between the age-isomerized βCTX fragment and the non-isomerized αCTX fragment. By measurement of TRACP activity, CTX release, number of TRACP positive cells and pit area/pit number, we evaluated osteoclastogenesis as well as osteoclast resorption on aged and young bones. We found that the αCTX / βCTX ratio is 3:1 in young compared to aged bones, and we found that both α and βCTX are released by osteoclasts during resorption. Osteoclastogenesis was augmented on aged compared to young bones, and the difference was enhanced under low serum conditions. We found that mature osteoclasts resorb more on aged than on young bone, despite unchanged adhesion and morphology. These data indicate that the age of the bone plays an important role in controlling osteoclast-mediated resorption, with significantly higher levels of osteoclast differentiation and resorption on aged bones when compared to young bones.
68 citations
"Nano-topography sensing by osteocla..." refers background in this paper
...For example, the resorptive activity of osteoclasts on old bone is substantially higher than that on new bone (Henriksen et al., 2007); moreover, the assembly of a sealing zone occurs on selective and confined areas within the osteoclastbone interface (Geblinger et al., 2009)....
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TL;DR: It is demonstrated that the fibers formed in vitro are highly similar to an FN matrix produced by cultured fibroblasts, and it is shown that the stretched FN fibrils can support cell adhesion, and display antigenic epitopes which appear to be sequestered in the relaxed molecules.
Abstract: Polymerization of fibronectin (FN) and its assembly into fibers, in vitro, is a two-step self-assembly process, initiated by the formation of a stable FN sheet made of globular particles at the air–liquid interface, and followed by shear-force driven fibrillogenesis along a superhydrophobic surface made of elastic micropillars. The initially-formed fibrils, displaying “rough” surfaces with globular subdomains, can be further stretched into “smooth” fibers with a characteristic diameter of 14 nm. Using high-resolution scanning electron microscopy, we demonstrated that the fibers formed in vitro are highly similar to an FN matrix produced by cultured fibroblasts. Furthermore, we showed that the stretched FN fibrils can support cell adhesion, and display antigenic epitopes which appear to be sequestered in the relaxed molecules. These findings suggest that cells are able to mechanically fine-tune the biological activity of the underlying matrix by modulating its structure, surface properties and organization.
57 citations
"Nano-topography sensing by osteocla..." refers background in this paper
...…underlying the cellular response to topographical features have been suggested for a variety of cell types (Balaban et al., 2001; Gov and Gopinathan, 2006; Patel et al., 2001; Riveline et al., 2001; Tarricone et al., 2001; Ulmer et al., 2008; Van Aelst et al., 1996; Vogel and Sheetz, 2006)....
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...Another possibility is that the topography of the surface induces conformational changes in proteins such as fibronectin that are adsorbed on the surface, thus exposing specific binding sites within the protein that are hidden when the protein is adsorbed on a flat surface (Ulmer et al., 2008)....
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TL;DR: In this study, surface modification methods for stainless steel, which is a representative metal for biomedical device, were developed and a hydrophilic and smooth surface was found to be the best of choice for decreasing the protein adsorption.
Abstract: Protein adsorption on a biomaterial surface is of great importance as it usually induces unfavorable biological cascades, with the result that much surface modification research has had to be performed in an effort to prevent this. In this study, we developed surface modification methods for stainless steel, which is a representative metal for biomedical device. The stainless steels were first smoothened to different extents by electropolishing, in order to obtain a rough or smooth surface. On these two kinds of substrates, we introduced epoxide groups to the metal surface by silanization with 3-glycidoxypropyltrimethoxysilane (GPTS). Then, various polymers such as poly(ethylene glycol) (PEG), poly(tetrahydrofuran glycol) (PTG), poly(propylene glycol) (PPG) and poly(dimethylsiloxane) (PDMS) were grafted on the silanized stainless steels. Each surface modification step was confirmed by various analytical methods. Contact angle measurement revealed that the surface hydrophilicity was controllable by polymer grafting. Root-mean-square (RMS) data of atomic force microscopy showed that surface roughness was dramatically changed by electropolishing. Based on these results, the correlation between surface properties and protein adsorption was investigated. In the protein adsorption study, we observed that all of the polymer-grafted stainless steels exhibited lower protein adsorption, when compared with bare stainless steel. Moreover, a hydrophilic and smooth surface was found to be the best of choice for decreasing the protein adsorption.
57 citations
"Nano-topography sensing by osteocla..." refers background in this paper
...The latter mechanism could be expected, considering the fact that rough surfaces characterized by high surface energy usually show stronger protein adsorption (Kang and Lee, 2007; Rechendorff et al., 2006)....
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