scholarly journals Surface electric fields increase human osteoclast resorption through improved wettability on carbonate-incorporated apatite

2021 ◽  
Author(s):  
Leire Bergara Muguruza ◽  
Keijo Makela ◽  
Tommi Yrjala ◽  
Jukka Salonen ◽  
Kimihiro Yamashita ◽  
...  
Keyword(s):  
Free Energy ◽  
Electric Fields ◽  
Bone Matrix ◽  
Surface Characteristics ◽  
Natural Mineral ◽  
Electrical Polarization ◽  
Mineral Phases ◽  
Human Osteoclast ◽  
Human Osteoclasts ◽  
Osteoclast Resorption

Osteoclast-mediated bioresorption can be of an efficient means of incorporating the dissolution of biomaterials in the bone remodeling process. Because of compositionally and structurally close resemblance of biomaterials with the natural mineral phases of the bone matrix, synthetic carbonate-substituted hydroxyapatite (CA) is considered as an ideal clinical biomaterial. The present study therefore investigated the effects of electrical polarization on the surface characteristics and interactions with human osteoclasts of hydroxyapatite (HA) and CA. Electrical polarization was found to improve the surface wettability of these materials by increasing the surface free energy, and this effect was maintained for one month. Analyses of human osteoclast cultures established that CA subjected to a polarization treatment accelerated osteoclast resorption but did not affect the early differentiation phase or the adherent morphology of the osteoclasts as evaluated by staining. These data suggest that the surface characteristics of the CA promoted osteoclast resorption. The results of this work are expected to contribute to the design of cell-mediated biomaterials that can be resorbed by osteoclasts after fulfilling their primary function as a scaffold for bone regeneration.

scholarly journals Surface Electric Fields Increase Human Osteoclast Resorption through Improved Wettability on Carbonate-Incorporated Apatite

2021 ◽  
Author(s):  
Leire Bergara-Muguruza ◽  
Keijo Mäkelä ◽  
Tommi Yrjälä ◽  
Jukka Salonen ◽  
Kimihiro Yamashita ◽  
...  
Keyword(s):  
Electric Fields ◽  
Human Osteoclast ◽  
Osteoclast Resorption

scholarly journals ‘Educated’ Osteoblasts Reduce Osteoclastogenesis in a Bone-Tumor Mimetic Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 263
Author(s):  
Alexus D. Kolb ◽  
Jinlu Dai ◽  
Evan T. Keller ◽  
Karen M. Bussard
Keyword(s):  
Bone Resorption ◽  
Bone Tumor ◽  
Bone Matrix ◽  
Necrosis Factor Alpha ◽  
Tumor Bearing ◽  
Receptor Activator ◽  
Factor Alpha ◽  
Osteoclast Resorption ◽  
Necrosis Factor

Breast cancer (BC) metastases to bone disrupt the balance between osteoblasts and osteoclasts, leading to excessive bone resorption. We identified a novel subpopulation of osteoblasts with tumor-inhibitory properties, called educated osteoblasts (EOs). Here we sought to examine the effect of EOs on osteoclastogenesis during tumor progression. We hypothesized that EOs affect osteoclast development in the bone-tumor niche, leading to suppressed pre-osteoclast fusion and bone resorption. Conditioned media (CM) was analyzed for protein expression of osteoclast factors receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα) via ELISA. EOs were co-cultured with pre-osteoclasts on a bone mimetic matrix to assess osteoclast resorption. Pre-osteoclasts were tri-cultured with EOs plus metastatic BC cells and assessed for tartrate-resistance acid phosphatase (TRAP)-positive, multinucleated (≥3 nuclei), mature osteoclasts. Tumor-bearing murine tibias were stained for TRAP to determine osteoclast number in-vivo. EO CM expressed reduced amounts of soluble TNFα and OPG compared to naïve osteoblast CM. Osteoclasts formed in the presence of EOs were smaller and less in number. Upon co-culture on a mimetic bone matrix, a 50% reduction in the number of TRAP-positive osteoclasts formed in the presence of EOs was observed. The tibia of mice inoculated with BC cells had less osteoclasts per bone surface in bones with increased numbers of EO cells. These data suggest EOs reduce osteoclastogenesis and bone resorption. The data imply EOs provide a protective effect against bone resorption in bone metastatic BC.

Alignment of carbon nanotubes under the influences of nematic liquid crystals and electric fields — an analytical study

2021 ◽  
Author(s):  
Setia Budi Sumandra ◽  
Bhisma Mahendra ◽  
Fahrudin Nugroho ◽  
Yusril Yusuf
Keyword(s):  
Carbon Nanotubes ◽  
Free Energy ◽  
Electric Field ◽  
Electric Fields ◽  
Analytical Study ◽  
Free Energy Density ◽  
Diameter Ratio ◽  
Order Parameters ◽  
Anchoring Strength ◽  
Length To Diameter Ratio

Carbon nanotubes (CNTs) have benefits in various fields, they are disadvantageous due to their tendency to form aggregates and poorly controlled alignment of the CNT molecules (characterized by order parameters). These deficiencies can be overcome by dispersing the CNTs in nematic liquid crystal (LC) and placing the mixture under the influence of an electric field. In this study, Doi and Landau–de Gennes free energy density equations are used to analytically confirm that an electric field increases the order parameters of CNTs and LCs in a dispersion mixture. The anchoring strength of the nematic LC is also found to affect the order parameters of the CNTs and LC. Further, increasing the length-to-diameter ratio of the CNTs increases their alignment without affecting the LC alignment. These findings indicate that CNT molecular alignment can be controlled by adjusting the CNT length-to-diameter ratio, anchoring the LCs, and adjusting the electric field strength.

Electroelastic Response of Isotropic Dielectric Elastomer Composites with Deformation-Dependent Apparent-Permittivity Matrix

2020 ◽  
Vol 87 (9) ◽  
Author(s):  
Victor Lefèvre
Keyword(s):  
Free Energy ◽  
Electric Fields ◽  
Dielectric Response ◽  
Dielectric Elastomer ◽  
Spherical Particles ◽  
Full Field ◽  
The Matrix ◽  
Elastomer Composites ◽  
Non Gaussian ◽  
Elastic Dielectric

Abstract This paper puts forth an approximate yet accurate free energy for the elastic dielectric response—under finite deformations and finite electric fields—of non-percolative dielectric elastomer composites made out of a non-Gaussian dielectric elastomer matrix with deformation-dependent apparent permittivity isotropically filled with nonlinear elastic dielectric particles that may exhibit polarization saturation. While the proposed free energy applies in its most general form to arbitrary isotropic non-percolative microstructures, closed-form specializations are recorded for the practically relevant cases of rigid or liquid-like spherical particles. The proposed free energy is exact by construction in the asymptotic context of small deformations and moderate electric fields and is shown to remain accurate for arbitrary large deformations and electric fields via comparisons with full-field finite-element simulations. The proposed constitutive model is deployed to probe the electrostriction response of these dielectric elastomer composites and corresponding results reveal that their elastic dielectric response strongly depends on the deformation-dependent apparent permittivity of the matrix they comprise.

Phase-Dield Simulation of Rhombohedral and Tetragonal Phases in Ferroelectric Single Crystals

Aerospace ◽  
2006 ◽  
Author(s):  
T. Liu ◽  
C. S. Lynch
Keyword(s):  
Free Energy ◽  
Phase Transformations ◽  
Single Crystals ◽  
Electric Fields ◽  
Tetragonal Phase ◽  
Ferroelectric Materials ◽  
Integration Scheme ◽  
Ferroelectric Crystal ◽  
Domain Structures ◽  
Tdgl Equation

Ferroelectric materials exhibit spontaneous polarization and domain structures below the Curie temperature. In this work the phase field approach has been used to simulate phase transformations and the formation of ferroelectric domain structures. The evolution of phases and domain structures was simulated in ferroelectric single crystals by solving the time dependent Ginzburg-Landau (TDGL) equation with polarization as the order parameter. In the TDGL equation the free energy of a ferroelectric crystal is written as a function of polarization and applied fields. Change of temperature as well as application of stress and electric fields leads to change of the free energy and evolution of phase states and domain structures. In this work the finite difference method was implemented for the spatial description of the polarization and the temporal evolution of polarization field was computed by solving the TDGL equation with an explicit time integration scheme. Cubic to tetragonal, cubic to rhombohedral and rhombohedral to tetragonal phase transformations were modeled, and the formation of domain structures was simulated. Field induced polarization switching and rhombohedral to tetragonal phase transition were simulated.

Targeting CD26 with Humanized Monoclonal Antibody, As a Novel Approach to Inhibit Human Osteoclast Differentiation and Subsequent Bone Resorption

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1348-1348
Author(s):  
Hiroko Nishida ◽  
Hiroko Madokoro ◽  
Hiroshi Suzuki ◽  
Michiie Sakamoto ◽  
Chikao Morimoto ◽  
...  
Keyword(s):  
Bone Metastasis ◽  
Therapeutic Potential ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Precursor Cells ◽  
Osteolytic Bone Metastasis ◽  
Human Osteoclast ◽  
And Function ◽  
Human Osteoclasts ◽  
Rankl Stimulation

Abstract Abstract 1348 Bone disease is a hallmark of malignancy with osteolytic bone metastasis, including multiple myeloma (MM) and targeting osteoclasts (OCs) to alleviate bone destruction is a component of the standard care for MM. CD26 is a 110-kDa multifunctional membrane-bound glycoprotein, with dipeptidyl peptidase IV (DPPIV) enzyme activity in its extracellular domain and is critical in T-cell activation and several tumor developments, including malignant lymphoma. However, little is known about the role of CD26 in regulating bone remodeling. In this study, we show that CD26 is expressed on normal human osteoclasts and moreover, intensely expressed on activated human osteoclasts with osteolytic bone metastasis, including MM. We explore the function of CD26 in osteoclastgenesis (OCG) and investigate the effects of humanized anti-CD26 monoclonal antibody (huCD26mAb), which has shown promising clinical activity in T-cell lymphoma, on human OC differentiation, maturation and function. We further define the molecular targets of CD26 signaling cascade in OCG and explore the therapeutic potential of huCD26mAb for treating osteolytic bone metastasis. Human bone marrow mononuclear cells (BMMs) were cultured with human M-CSF (25ng/ml) plus sRANKL (50ng/ml) in the absence or presence of huCD26mAb for the indicated times. Then, M-CSF and sRANKL stimulate CD26 expressions during OCG, in a dose-dependent manner. The expression of CD26 up-regulates mitogen-activated protein kinase14 (p38MAPK) phosphorylation. P38MAPK phosphorylation also occurs downstream of RANK signaling in OCs and stimulates its downstream activation of microphthalmia-associated transcription factor (mi/Mitf), which plays an important role in OC function. Importantly, huCD26mAb decreased the number of multinucleated OCs (>3 nuclei) by tartrate-resistant phosphates (TRAP)/CD26 staining and the secretion of TRAP-5b and type 1 collagen; specific mature OC markers. It decreased the size of OCs and the number of nuclei per OC, with significantly defective bone resorption activity, as evidenced by diminished pit formation on fluoresceinated calcium phosphate-coated plates. In contrast, huCD26mAb added after 4- or 7- days' BMM cultures with M-CSF plus sRANKL did not have significant effects on mature osteoclast formation and function. Given these dual roles of CD26 in OCG, we next examined the effects of huCD26mAb on the phosphorylation of p38MAPK in OC precursor cells and mature OCs. At first, in the absence of huCD26mAb, similar amounts of p38MAPK and MKK3/6 (a molecule that is upstream of p38MAPK) were present in OC precursor cells and OCs. In response to RANKL, MKK3/6-p38MAPK was phosphorylated within 15 minutes in OC precursor cells and reached a maximal level within 30 minutes, and was maintained up to 60 minutes. Moreover, mi/Mitf was subsequently rapidly activated and persisted for 24hours. In the presence of huCD26mAb, when huCD26mAb bound to CD26 on OC precursor cells, only the MKK3/6-p38MAPK pathway was specifically rapidly inactivated, as shown by the persistent decrease in the phosphorylation of p38MAPK, together with MKK3/6, starting within 15 minutes of RANKL stimulation. Subsequent mi/Mitf phosphorylation was also persistently inhibited. In contrast, MKK3/6-p38MAPK was not phosphorylated at all in mature OCs after RANKL stimulation, regardless of the absence or presence of huCD26mAb. These results suggest that huCD26mAb suppressed RANKL induced p38MAPK phosphorylation in OC precursor cells, but not in OCs. The activation of other MAPKs including ERK and SAPK/JNK, or NFκB were rapidly induced in response to RANKL both in OC precursor cells and OCs, regardless of the absence or presence of huCD26mAb. Moreover, p38MAPK inhibitor also strongly inhibited OC formation and function through the suppression of p38 MAPK phosphorylation and subsequent mi/Mitf activation in OC precursor cells, but not in OCs. In conclusion, these data demonstrate that targeting CD26 on OC precursor cells with huCD26mAb suppressed human osteoclast differentiation, via the inhibition of MKK3/6-p38MAPK-mi/Mitf phosphorylation pathway and impaired subsequent mature osteoclast formation and function. Our results strongly suggest that targeting OCs with huCD26mAb has a promising alternative therapeutic potential for the treatment of osteolytic bone metastasis, including MM, to reduce the occurrence of total skeletal-related events. Disclosures: No relevant conflicts of interest to declare.

Effects of local electric fields on the redox free energy of single stranded DNA

2011 ◽  
Vol 47 (9) ◽  
pp. 2646-2648 ◽  
Author(s):  
Marco D'Abramo ◽  
Modesto Orozco ◽  
Andrea Amadei
Keyword(s):  
Free Energy ◽  
Electric Fields ◽  
Single Stranded Dna

scholarly journals Electrical unfolding of cytochrome c during translocation through a nanopore constriction

2021 ◽  
Vol 118 (17) ◽  
pp. e2016262118
Author(s):  
Prabhat Tripathi ◽  
Abdelkrim Benabbas ◽  
Behzad Mehrafrooz ◽  
Hirohito Yamazaki ◽  
Aleksei Aksimentiev ◽  
...  
Keyword(s):  
Free Energy ◽  
Electric Field ◽  
Electric Fields ◽  
Driving Force ◽  
Protein Translocation ◽  
Critical Factors ◽  
Unfolded Protein ◽  
Small Proteins ◽  
Unfolded State ◽  
Cellular Compartments

Many small proteins move across cellular compartments through narrow pores. In order to thread a protein through a constriction, free energy must be overcome to either deform or completely unfold the protein. In principle, the diameter of the pore, along with the effective driving force for unfolding the protein, as well as its barrier to translocation, should be critical factors that govern whether the process proceeds via squeezing, unfolding/threading, or both. To probe this for a well-established protein system, we studied the electric-field–driven translocation behavior of cytochrome c (cyt c) through ultrathin silicon nitride (SiNx) solid-state nanopores of diameters ranging from 1.5 to 5.5 nm. For a 2.5-nm-diameter pore, we find that, in a threshold electric-field regime of ∼30 to 100 MV/m, cyt c is able to squeeze through the pore. As electric fields inside the pore are increased, the unfolded state of cyt c is thermodynamically stabilized, facilitating its translocation. In contrast, for 1.5- and 2.0-nm-diameter pores, translocation occurs only by threading of the fully unfolded protein after it transitions through a higher energy unfolding intermediate state at the mouth of the pore. The relative energies between the metastable, intermediate, and unfolded protein states are extracted using a simple thermodynamic model that is dictated by the relatively slow (∼ms) protein translocation times for passing through the nanopore. These experiments map the various modes of protein translocation through a constriction, which opens avenues for exploring protein folding structures, internal contacts, and electric-field–induced deformability.

scholarly journals Cobalt-containing Calcium Phosphate Induces Resorption of Biomineralized Collagen by Human Osteoclasts

2020 ◽  
Author(s):  
Daniel de Melo Pereira ◽  
Matthias Schumacher ◽  
Pamela Habibović
Keyword(s):  
Cell Culture ◽  
Calcium Phosphate ◽  
Calcium Release ◽  
Type I Collagen ◽  
Cell Culture Supernatant ◽  
Type I ◽  
Cobalt Ions ◽  
Collagen Membranes ◽  
Human Osteoclasts ◽  
Osteoclast Resorption

Abstract Background: Biomineralized collagen, consisting of fibrillary type-I collagen with embedded hydroxyapatite mineral, is a bone-mimicking material with potential application as a bone graft substitute. Despite the chemical and structural similarity with bone extracellular matrix, no evidence exists so far that biomineralized collagen can be resorbed by osteoclasts. The aim of the current study was to induce resorption of biomineralized collagen by osteoclasts by a two-fold modification: increasing the calcium phosphate content and introducing cobalt ions (Co2+), which have been previous shown to stimulate resorptive activity of osteoclasts.Methods: To this end, we produced biomineralized collagen membranes and coated them with a cobalt-containing calcium phosphate (CoCaP). Human osteoclasts, derived from CD14+ monocytes from peripheral blood, were differentiated directly on the membranes. Their morphology was assessed by laser confocal microscopy and their capacity for resorption observed by scanning electron microscopy (SEM), as well as indirectly quantified by calcium release into cell culture supernatant. Results: The CoCaP coating increased the mineral content of the membranes by 4 wt.% and their elastic modulus from 1 to 10 MPa. The coated membranes showed a sustained Co2+ release of about 7 nM per 2 days. In contrast to uncoated membranes, on CoCaP-coated biomineralized collagen membranes, osteoclasts sporadically formed actin rings, and caused resorption lacunae to form, as observed by SEM and confirmed by increase in Ca2+ concentration in cell culture medium. The effect of the CoCaP layer on osteoclast function is thought to be mainly caused by the increase of membrane stiffness, although the effect of Co2+, which was released in very low amounts, cannot be fully excluded.Conclusions: This work shows the potential of this relatively simple approach to induce osteoclast resorption of biomineralized collagen, despite the fact that the extent of osteoclast resorption was limited, and the method needs further optimization,. Moreover, the coating method is suitable for incorporating bioactive ions of interest into biomineralized collagen, which is typically not possible using the common biomineralization methods, such as polymer-induced liquid precursor method.

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