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Journal ArticleDOI

Nano-topography sensing by osteoclasts.

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.
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 ArticleDOI
TL;DR: A correlative imaging method that enables monitoring of the same area of bone surface by time-lapse light microscopy, electron microscope, and atomic force microscopy before, during, and after exposure to osteoclasts is designed and implemented.
Abstract: Bone remodeling relies on the coordinated functioning of osteoblasts, bone-forming cells, and osteoclasts, bone-resorbing cells. The effects of specific chemical and physical bone features on the osteoclast adhesive apparatus, the sealing zone ring, and their relation to resorption functionality are still not well-understood. We designed and implemented a correlative imaging method that enables monitoring of the same area of bone surface by time-lapse light microscopy, electron microscopy, and atomic force microscopy before, during, and after exposure to osteoclasts. We show that sealing zone rings preferentially develop around surface protrusions, with lateral dimensions of several micrometers, and ∼1 μm height. Direct overlay of sealing zone rings onto resorption pits on the bone surface shows that the rings adapt to pit morphology. The correlative procedure presented here is noninvasive and performed under ambient conditions, without the need for sample labeling. It can potentially be applied to study ...

13 citations

Journal ArticleDOI
TL;DR: A review of recent developments in such applied strategies can be found in this paper, where various approaches, such as the modification of chemical/structural characteristics or the incorporation of bioactive molecules, have been employed in order to modulate the crosstalk with the immune cells.
Abstract: The critical role of the immune system in host defense against foreign bodies and pathogens has been long recognized. With the introduction of a new field of research called osteoimmunology, the crosstalk between the immune and bone-forming cells has been studied more thoroughly, leading to the conclusion that the two systems are intimately connected through various cytokines, signaling molecules, transcription factors and receptors. The host immune reaction triggered by biomaterial implantation determines the in vivo fate of the implant, either in new bone formation or in fibrous tissue encapsulation. The traditional biomaterial design consisted in fabricating inert biomaterials capable of stimulating osteogenesis; however, inconsistencies between the in vitro and in vivo results were reported. This led to a shift in the development of biomaterials towards implants with osteoimmunomodulatory properties. By endowing the orthopedic biomaterials with favorable osteoimmunomodulatory properties, a desired immune response can be triggered in order to obtain a proper bone regeneration process. In this context, various approaches, such as the modification of chemical/structural characteristics or the incorporation of bioactive molecules, have been employed in order to modulate the crosstalk with the immune cells. The current review provides an overview of recent developments in such applied strategies.

13 citations

Journal ArticleDOI
06 Mar 2019
TL;DR: The effects of osteoporosis and bisphosphonates on osseointegration of titanium (Ti) implants with microstructured surfaces, which have been shown to support osteoblast differentiation in vitro and rapid osseointedegration in vivo, are assessed.
Abstract: Excessive decreases in bone volume (BV) and bone mineral density (BMD) can lead to osteoporosis, potentially hindering implant osseointegration. Bisphosphonates are commonly used to combat osteoporosis by slowing osteoclast-mediated resorption; however, functional osteoclasts are integral to bone remodeling and, thus, implant osseointegration, potentially contraindicating bisphosphonate use during implantation. To optimize the use of implant technologies in patients with compromised bone structure and metabolism, we need a more complete understanding of the biological response to surface design. The goal of this study was to assess the effects of osteoporosis and bisphosphonates on osseointegration of titanium (Ti) implants with microstructured surfaces, which have been shown to support osteoblast differentiation in vitro and rapid osseointegration in vivo. Forty, 8-month-old, virgin, female CD Sprague Dawley rats underwent ovariectomy (OVX) or sham (SHOVX) surgery. After 5 weeks, animals were injected subcutaneously with either the bisphosphonate (BIS), Ibandronate (25 µg/kg), or phosphate-buffered saline (PBS) every 25 days. 1 week after the initial injection, O2.5mm × 3.5mm microrough (SLA; grit-blasted/acid etched) implants were placed transcortically in the distal metaphysis of each femur resulting in four groups: 1) SHOVX+PBS; 2) SHOVX+BIS; 3) OVX+PBS; and 4) OVX+BIS. After 28d, qualitative properties of the bone and implant osseointegration were assessed using micro-computed tomography (microCT), calcified histomorphometry (Van Gieson's stain), and removal torque testing. microCT revealed decreased bone volume in OVX rats, which was slowed by bisphosphonate treatment. Reduced bone-to-implant contact (BIC) was evident in OVX+PBS compared to SHOVX+PBS. Although BV/TV was increased in OVX+BIS compared to OVX+PBS, bisphosphonate treatment had no effect on BIC. Removal torque testing revealed a higher maximum torque, torsional stiffness, and torsional energy in SHOVX compared to OVX with no effects due to bisphosphonate treatment. Our results show that osseointegration is decreased in osteoporotic animals. Ibandronate halts the progression of osteoporosis but does not enhance osseointegration. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

13 citations


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

  • ...During remodeling, osteoclasts resorb a volume of bone leaving behind a foundation with a specific chemistry,((8)) stiffness,((9)) and morphology((10)) for osteoblasts to synthesize and calcify their matrix....

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Journal ArticleDOI
TL;DR: The secondary fusion of osteoclasts uses actin-based superstructures for cell-cell interactions before the definitive fusion of the plasma membranes.
Abstract: We previously reported the transient appearance of an actin superstructure, called the zipper-like structure, during the primary fusion (fusion of mononuclear precursors) and the secondary fusion (fusion of multinucleated cells) of osteoclasts. Here, we focus on the actin-based superstructures that link two precursor cells during the secondary fusion event. In one type of secondary fusion, the osteoclasts transformed the podosome belts into the zipper-like structure at the site of cell contact and the apposed plasma membranes in the zipper-like structure attached to each other via a discontinuous interface. In another type of secondary fusion, the osteoclasts used a filopodium-like protrusion that linked the two cells. Both types of cell fusion required a lag period between the adhesion of the cells and the fusion of cell bodies. Thus, the secondary fusion of osteoclasts uses actin-based superstructures for cell-cell interactions before the definitive fusion of the plasma membranes.

12 citations

Journal ArticleDOI
TL;DR: Geologic hydroxyapatite (HAP), closely related to bone apatite, is used to investigate how HAP surface chemistry and nano/microscale topography individually influence the crystal-protein interface, and how the altered protein deposition impacts subsequent breast cancer cell activities.

11 citations


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

  • ...Later, geologic calcite single crystals with identical surface chemistry but different surface roughness were used as model substrates for studying nano-topography sensing by osteoclasts [48]....

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References
More filters
Journal ArticleDOI
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.

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 ArticleDOI
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.
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.

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)....

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Journal ArticleDOI
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.
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.

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…...

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Journal ArticleDOI
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.

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 ArticleDOI
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.
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.

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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