scholarly journals A New Piezoelectric Actuator Induces Bone FormationIn Vivo: A Preliminary Study

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Joana Reis ◽  
Clara Frias ◽  
Carlos Canto e Castro ◽  
Maria Luísa Botelho ◽  
António Torres Marques ◽  
...  
Keyword(s):  
Piezoelectric Actuator ◽  
Polyvinylidene Fluoride ◽  
Bone Growth ◽  
Piezoelectric Effect ◽  
Biological Response ◽  
Nuclear Antigen ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Area ◽  
Converse Piezoelectric Effect

Thisin vivostudy presents the preliminary results of the use of a novel piezoelectric actuator for orthopedic application. The innovative use of the converse piezoelectric effect to mechanically stimulate bone was achieved with polyvinylidene fluoride actuators implanted in osteotomy cuts in sheep femur and tibia. The biological response around the osteotomies was assessed through histology and histomorphometry in nondecalcified sections and histochemistry and immunohistochemistry in decalcified sections, namely, through Masson's trichrome, and labeling of osteopontin, proliferating cell nuclear antigen, and tartrate-resistant acid phosphatase. After one-month implantation, total bone area and new bone area were significantly higher around actuators when compared to static controls. Bone deposition rate was also significantly higher in the mechanically stimulated areas. In these areas, osteopontin increased expression was observed. The presentin vivostudy suggests that piezoelectric materials and the converse piezoelectric effect may be used to effectively stimulate bone growth.

scholarly journals The Structure and Properties of Electroceramics for Bone Graft Substitution

2007 ◽  
Vol 361-363 ◽  
pp. 99-102 ◽  
Author(s):  
F.R. Baxter ◽  
I.G. Turner ◽  
Chris R. Bowen ◽  
J.P. Gittings ◽  
J.B. Chaudhuri ◽  
...  
Keyword(s):  
Grain Size ◽  
Barium Titanate ◽  
Bone Growth ◽  
Piezoelectric Properties ◽  
Piezoelectric Effect ◽  
Positive Influence ◽  
Sem Analysis ◽  
A Value ◽  
Piezoelectric Constants

Hydroxyapatite (HA) and barium titanate (BT) powders were mixed and sintered to form hydroxyapatite – barium titanate (HABT) ceramics. These materials were then poled and their piezoelectric properties were measured. The microstructure of unpoled samples was examined using scanning electron microscopy (SEM).The piezoelectric constants (d33 and d31) of the ceramics were found to be dependent on the proportion of BT in the ceramic In materials containing less than 70% BT, no piezoelectric effect was found. Above this value, the piezoelectric constant increased with the addition of BT up to a value of 108pCN-1 for pure BT. Values of d33 for ceramics containing more than 80% BT are above values previously shown to have a positive influence on bone growth in vivo. SEM analysis indicated that the grain size within the materials decreased as the proportion of BT in the material was reduced. Examination of the microstructure of the ceramics indicated the presence of electrical domains in the 100% BT and 95% BT ceramics. Domains were not visible below 95% BT. The reduction in grain size may influence the reduction in piezoelectric activity within the materials but cannot be considered to be the only cause.

Intense Static Magnetic Field Induced Bone Growth in Vivo

1984 ◽  
Vol 3 (1) ◽  
pp. 223-234
Author(s):  
Frank Papatheofanis ◽  
Bill Fapatheofanls ◽  
Robert Ray
Keyword(s):  
Magnetic Field ◽  
Static Magnetic Field ◽  
Bone Growth

Structural-parametric model of an electroelastic actuator for nanomechanics

2020 ◽  
pp. 3-11
Author(s):  
S.M. Afonin
Keyword(s):  
Transfer Function ◽  
Piezoelectric Actuator ◽  
Transfer Functions ◽  
Piezoelectric Effect ◽  
Parametric Model ◽  
Elastic Compliance ◽  
Parametric Models ◽  
Piezo Actuator ◽  
Structural Scheme ◽  
Model Transfer

Structural-parametric models, structural schemes are constructed and the transfer functions of electro-elastic actuators for nanomechanics are determined. The transfer functions of the piezoelectric actuator with the generalized piezoelectric effect are obtained. The changes in the elastic compliance and rigidity of the piezoactuator are determined taking into account the type of control. Keywords electro-elastic actuator, piezo actuator, structural-parametric model, transfer function, parametric structural scheme

scholarly journals The application prospect of metal/metal oxide nanoparticles in the treatment of osteoarthritis

2021 ◽  
Vol 394 (10) ◽  
pp. 1991-2002
Author(s):  
Junchao Luo ◽  
Yin Zhang ◽  
Senbo Zhu ◽  
Yu Tong ◽  
Lichen Ji ◽  
...  
Keyword(s):  
Metal Oxide ◽  
Metal Oxide Nanoparticles ◽  
Biological Response ◽  
Cell Uptake ◽  
Oxide Nanoparticles ◽  
Therapeutic Effects ◽  
Superoxide Anions ◽  
Metal Metal ◽  
Cartilage Wear

AbstractThe current understanding of osteoarthritis is developing from a mechanical disease caused by cartilage wear to a complex biological response involving inflammation, oxidative stress and other aspects. Nanoparticles are widely used in drug delivery due to its good stability in vivo and cell uptake efficiency. In addition to the above advantages, metal/metal oxide NPs, such as cerium oxide and manganese dioxide, can also simulate the activity of antioxidant enzymes and catalyze the degradation of superoxide anions and hydrogen peroxide. Degrading of metal/metal oxide nanoparticles releases metal ions, which may slow down the progression of osteoarthritis by inhibiting inflammation, promoting cartilage repair and inhibiting cartilage ossification. In present review, we focused on recent research works concerning osteoarthritis treating with metal/metal oxide nanoparticles, and introduced some potential nanoparticles that may have therapeutic effects.

scholarly journals Estrogen Decreases Cytoskeletal Organization by Forming an ERα/SHP2/c-Src Complex in Osteoclasts to Protect against Ovariectomy-Induced Bone Loss in Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 619
Author(s):  
Hyun-Jung Park ◽  
Malihatosadat Gholam-Zadeh ◽  
Sun-Young Yoon ◽  
Jae-Hee Suh ◽  
Hye-Seon Choi
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Ring Formation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Actin Ring ◽  
Collagen Crosslinks ◽  
Trap Staining ◽  
Src Activation

Loss of ovarian function is closely related to estrogen (E2) deficiency, which is responsible for increased osteoclast (OC) differentiation and activity. We aimed to investigate the action mechanism of E2 to decrease bone resorption in OCs to protect from ovariectomy (OVX)-induced bone loss in mice. In vivo, tartrate-resistant acid phosphatase (TRAP) staining in femur and serum carboxy-terminal collagen crosslinks-1 (CTX-1) were analyzed upon E2 injection after OVX in mice. In vitro, OCs were analyzed by TRAP staining, actin ring formation, carboxymethylation, determination of reactive oxygen species (ROS) level, and immunoprecipitation coupled with Western blot. In vivo and in vitro, E2 decreased OC size more dramatically than OC number and Methyl-piperidino-pyrazole hydrate dihydrochloride (MPPD), an estrogen receptor alpha (ERα) antagonist, augmented the OC size. ERα was found in plasma membranes and E2/ERα signaling affected receptor activator of nuclear factor κB ligand (RANKL)-induced actin ring formation by rapidly decreasing a proto-oncogene tyrosine-protein kinase, cellular sarcoma (c-Src) (Y416) phosphorylation in OCs. E2 exposure decreased physical interactions between NADPH oxidase 1 (NOX1) and the oxidized form of c-Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), leading to higher levels of reduced SHP2. ERα formed a complex with the reduced form of SHP2 and c-Src to decrease c-Src activation upon E2 exposure, which blocked a signal for actin ring formation by decreased Vav guanine nucleotide exchange factor 3 (Vav3) (p–Y) and Ras-related C3 botulinum toxin substrate 1 (Rac1) (GTP) activation in OCs. E2/ERα signals consistently inhibited bone resorption in vitro. In conclusion, our study suggests that E2-binding to ERα forms a complex with SHP2/c-Src to attenuate c-Src activation that was induced upon RANKL stimulation in a non-genomic manner, resulting in an impaired actin ring formation and reducing bone resorption.

scholarly journals Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL

2021 ◽  
Vol 22 (1) ◽  
pp. 434
Author(s):  
Yuria Jang ◽  
Hong Moon Sohn ◽  
Young Jong Ko ◽  
Hoon Hyun ◽  
Wonbong Lim
Keyword(s):  
Nuclear Translocation ◽  
Critical Role ◽  
Osteoclast Differentiation ◽  
Point Mutations ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mice Model ◽  
Gsk 3Β ◽  
Rank Signaling

Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.

scholarly journals 'Off-the-shelf’ allogeneic antigen-specific adoptive T-cell therapy for the treatment of multiple EBV-associated malignancies

2021 ◽  
Vol 9 (2) ◽  
pp. e001608
Author(s):  
Debottam Sinha ◽  
Sriganesh Srihari ◽  
Kirrliee Beckett ◽  
Laetitia Le Texier ◽  
Matthew Solomon ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Adoptive T Cell Therapy ◽  
Nuclear Antigen ◽  
T Cell Therapy ◽  
In Vivo Models ◽  
Hla Alleles ◽  
Cell Therapies ◽  
Wide Range

BackgroundEpstein-Barr virus (EBV), an oncogenic human gammaherpesvirus, is associated with a wide range of human malignancies of epithelial and B-cell origin. Recent studies have demonstrated promising safety and clinical efficacy of allogeneic ‘off-the-shelf’ virus-specific T-cell therapies for post-transplant viral complications.MethodsTaking a clue from these studies, we developed a highly efficient EBV-specific T-cell expansion process using a replication-deficient AdE1-LMPpoly vector that specifically targets EBV-encoded nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2), expressed in latency II malignancies.ResultsThese allogeneic EBV-specific T cells efficiently recognized human leukocyte antigen (HLA)-matched EBNA1-expressing and/or LMP1 and LMP2-expressing malignant cells and demonstrated therapeutic potential in a number of in vivo models, including EBV lymphomas that emerged spontaneously in humanized mice following EBV infection. Interestingly, we were able to override resistance to T-cell therapy in vivo using a ‘restriction-switching’ approach, through sequential infusion of two different allogeneic T-cell therapies restricted through different HLA alleles. Furthermore, we have shown that inhibition of the programmed cell death protein-1/programmed death-ligand 1 axis in combination with EBV-specific T-cell therapy significantly improved overall survival of tumor-bearing mice when compared with monotherapy.ConclusionThese findings suggest that restriction switching by sequential infusion of allogeneic T-cell therapies that target EBV through distinct HLA alleles may improve clinical response.

scholarly journals Targeting of p38 Mitogen-Activated Protein Kinases to MEF2 Transcription Factors

1999 ◽  
Vol 19 (6) ◽  
pp. 4028-4038 ◽  
Author(s):  
Shen-Hsi Yang ◽  
Alex Galanis ◽  
Andrew D. Sharrocks
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Map Kinases ◽  
Biological Response ◽  
Extracellular Signals ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Mitogen-activated protein (MAP) kinase-mediated signalling to the nucleus is an important event in the conversion of extracellular signals into a cellular response. However, the existence of multiple MAP kinases which phosphorylate similar phosphoacceptor motifs poses a problem in maintaining substrate specificity and hence the correct biological response. Both the extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) subfamilies of MAP kinases use a second specificity determinant and require docking to their transcription factor substrates to achieve maximal substrate activation. In this study, we demonstrate that among the different MAP kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38α and p38β2. The efficiency of phosphorylation in vitro and transcriptional activation in vivo of MEF2A and MEF2C by these p38 subtypes requires the presence of a kinase docking domain (D-domain). Furthermore, the D-domain from MEF2A is sufficient to confer p38 responsiveness on different transcription factors, and reciprocal effects are observed upon the introduction of alternative D-domains into MEF2A. These results therefore contribute to our understanding of signalling to MEF2 transcription factors and demonstrate that the requirement for substrate binding by MAP kinases is an important facet of three different subclasses of MAP kinases (ERK, JNK, and p38).

DOES FAST EMBRYONIC BONE GROWTH TENSION THE PERIOSTEUM IN VIVO?

2008 ◽  
Vol 41 ◽  
pp. S52
Author(s):  
Jasper Foolen ◽  
Corrinus C van Donkelaar ◽  
Rik Huiskes ◽  
Keita Ito
Keyword(s):  
Bone Growth ◽  
Embryonic Bone
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