scholarly journals A Modified Murine Calvarial Osteolysis Model Exposed to Ti Particles in Aseptic Loosening

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Zhantao Deng ◽  
Shuai Wang ◽  
Mengyuan Li ◽  
Guangtao Fu ◽  
Chang Liu ◽  
...  
Keyword(s):  
Bone Loss ◽  
Aseptic Loosening ◽  
Tartrate Resistant Acid Phosphatase ◽  
Micro Ct ◽  
Calvarial Bone ◽  
X Ray ◽  
Severe Bone Loss ◽  
Trap Staining ◽  
Ti Particles

Aim. To investigate the different effects on osteolysis between commercial pure Ti particles and TiAl6V4 particles obtained from prosthesis of patients with aseptic loosening. Method. Scanning electron microscope, energy dispersive X-ray spectrometry, and X-ray diffraction were used for the size test, chemical composition test, and phase analysis of two kinds of Ti particles. Microcomputed tomography (micro-CT) and 3-dimensional reconstruction analysis were applied to analyze the bone loss quantitatively and radiologically. Hematoxylin-eosin (HE) staining and tartrate-resistant acid phosphatase (TRAP) staining were used to assess the histologic difference. Result. TiAl6V4 particles were constituted by FeO, Al45V7, and Al3Ti while pure Ti particles were constituted by Ti, Ti3O, and C4H7NO3. Similar particle size of nanoscale was detected of two Ti particles. A TiAl6V4 osteolysis model had more severe bone loss when scanned with micro-CT and assessed by quantitative analysis. TiAl6V4 also presented deeper and wider calvarial bone loss in HE staining and more activated osteoclasts in TRAP staining. Conclusion. A mouse calvarial model is the most effective animal model for the primary in vivo research of aseptic loosening. Compared with commercial Ti particles, TiAl6V4 particles derived from prosthesis of an aseptic loosening patient had more severe bone loss and more activated osteoclast, which was more consistent with pathogenesis of aseptic loosening in vivo, had high success rate of establishment of a model, and was more desired in animal modeling.

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 Dauricine Protects from LPS-Induced Bone Loss via the ROS/PP2A/NF-κB Axis in Osteoclasts

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 588 ◽  
Author(s):  
Hyun-Jung Park ◽  
Malihatosadat Gholam Zadeh ◽  
Jae-Hee Suh ◽  
Hye-Seon Choi
Keyword(s):  
Reactive Oxygen Species ◽  
Bone Loss ◽  
Nuclear Localization ◽  
Therapeutic Potential ◽  
Isoquinoline Alkaloid ◽  
Tartrate Resistant Acid Phosphatase ◽  
Oxygen Species ◽  
Trap Staining

Dauricine (DAC), an isoquinoline alkaloid, exhibits anti-inflammatory activity. We hypothesized that DAC may prevent the inflammatory bone loss induced by lipopolysaccharide (LPS). LPS-induced bone loss was decreased by DAC in female C57BL/6J mice as evaluated by micro-computerized tomography (μCT) analysis. In vivo tartrate-resistant acid phosphatase (TRAP) staining showed that the increased number of osteoclasts (OCs) in LPS-treated mice was attenuated by DAC, indicating that DAC exhibited bone sparing effects through acting on OCs. DAC also decreased the differentiation and activity of OCs after LPS stimulation in vitro. LPS-induced cytosolic reactive oxygen species (cROS) oxidized PP2A, a serine/threonine phosphatase, leading to the activation of IKKα/β, followed by the nuclear localization of p65. DAC decreased LPS-induced ROS, resulting in the recovery of the activity of PP2A by reducing its oxidized form. Consequently, DAC reduced the phosphorylation of IKKα/β to block the nuclear localization of p65, which decreased NF-κB activation. Taken together, DAC reduced the differentiation and activity of OCs by decreasing ROS via the ROS/PP2A/NF-κB axis, resulting in protection from LPS-induced bone loss. We have demonstrated that LPS-induced bone loss was inhibited by DAC via its action on OCs, implying the therapeutic potential of DAC against inflammatory bone loss.

scholarly journals Anti-Osteoporosis Effects of the Eleutherococcus senticosus, Achyranthes japonica, and Atractylodes japonica Mixed Extract Fermented with Nuruk

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3904
Author(s):  
So Young Eun ◽  
Yoon-Hee Cheon ◽  
Gyeong Do Park ◽  
Chong Hyuk Chung ◽  
Chang Hoon Lee ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Diseases ◽  
Marker Genes ◽  
Tartrate Resistant Acid Phosphatase ◽  
Specific Marker ◽  
Eleutherococcus Senticosus ◽  
Achyranthes Japonica ◽  
Atractylodes Japonica

Vigeo is a mixture of fermented extracts of Eleutherococcus senticosus Maxim (ESM), Achyranthes japonica (Miq.) Nakai (AJN), and Atractylodes japonica Koidzumi (AJK) manufactured using the traditional Korean nuruk fermentation method. Although the bioactive effects of ESM, AJN, and AJK have already been reported, the pharmacological effects of Vigeo have not been proven. Therefore, in this study, we investigated whether Vigeo had inhivitory effects on lipopolysaccharide (LPS)-induced inflammatory bone loss in vivo and receptor activator of nuclear factor-B ligand (RANKL)-induced osteoclastogenesis and the related mechanism in vitro. Vigeo administration conferred effective protection against bone loss induced by excessive inflammatory response and activity of osteoclasts in LPS-induced inflammatory osteoporosis mouse model. In addition, Vigeo significantly suppressed the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by RANKL and inhibited F-actin formation and bone resorbing activity without any cytotoxicity. Moreover, Vigeo significantly inhibited RANKL-induced phosphorylation of p38, ERK, JNK, IκB, and AKT and degradation of IkB. Additionally, Vigeo strongly inhibited the mRNA and protein expression of c-FOS and NFATc1 and subsequently attenuated the expression of osteoclast specific marker genes induced by RANKL. We demonstrated for the first time the anti-osteoporosis effect of Vigeo, suggesting that it could be a potential therapeutic candidate for the treatment of osteoclast-mediated inflammatory bone diseases.

scholarly journals Development of ultrafast laser-based x-ray in-vivo phase-contrast micro-CT beamline for biomedical applications at Advanced Laser Light Source (ALLS)

2008 ◽  
Author(s):  
Russell Kincaid ◽  
Andrzej Krol ◽  
Sylvain Fourmaux ◽  
Jean-Claude Kieffer ◽  
Cristina Serbanescu ◽  
...  
Keyword(s):  
Light Source ◽  
Biomedical Applications ◽  
Phase Contrast ◽  
Laser Light ◽  
Ultrafast Laser ◽  
Micro Ct ◽  
X Ray ◽  
Laser Light Source

Laser preconditioning of calvarial bone prior to an X-ray radiation injury: A preliminary in vivo study of the vascular response

2008 ◽  
Vol 40 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Sophie O. Desmons ◽  
Caroline J. Delfosse ◽  
Philippe Rochon ◽  
Bruno Buys ◽  
Guillaume Penel ◽  
...  
Keyword(s):  
Radiation Injury ◽  
In Vivo Study ◽  
Vascular Response ◽  
Calvarial Bone ◽  
X Ray

scholarly journals Contribution of Interleukin-11 and Prostaglandin(s) in Lipopolysaccharide-Induced Bone Resorption In Vivo

2002 ◽  
Vol 70 (7) ◽  
pp. 3915-3922 ◽  
Author(s):  
Li Li ◽  
Alireza Khansari ◽  
Lior Shapira ◽  
Dana T. Graves ◽  
Salomon Amar
Keyword(s):  
Bone Resorption ◽  
Subcutaneous Tissue ◽  
Interleukin 1 ◽  
Control Group ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Low Doses ◽  
Wild Type ◽  
Calvarial Bone

ABSTRACT We previously demonstrated that interleukin-1 (IL-1) and tumor necrosis factor (TNF) activities only partially account for calvarial bone resorption induced by local application of lipopolysaccharide (LPS) in mice. The present study was undertaken to determine the role and relative contribution of IL-11 and prostaglandin(s) (PG[s]) in LPS-induced bone resorption in vivo. A one-time dose of LPS was injected into the subcutaneous tissue overlying calvaria of mice lacking IL-1 receptor type I (IL-1RI−/−), mice lacking TNF receptor p55 and IL-1RI (TNFRp55−/−-IL-1RI−/−), and wild-type mice. Mice were then treated with injections of anti-IL-11 monoclonal antibody (MAb), indomethacin, or phosphate-buffered saline (PBS) and sacrificed 5 days later. Histological sections stained for tartrate-resistant acid phosphatase (TRAP) were quantified by histomorphometric analysis. At low doses of LPS (100 μg/mouse), the percentages of bone surface covered by osteoclasts were found to be similar in three strains of mice. The increase was reduced by 37% with anti-IL-11 MAb and by 46% with indomethacin. At higher doses of LPS (500 μg/mouse), we found an eightfold increase in these percentages in wild-type mice and a fivefold increase in these percentages in IL-1RI−/− and TNFRp55−/−−IL-1RI−/− mice after normalizing with the value from the saline-PBS control group in the same strain of mice. The increase was reduced by 55 and 69% in wild-type mice and by 50 and 57% in IL-1RI−/− and TNFRp55−/−−IL-1RI−/− mice treated with anti-IL-11 MAb or indomethacin, respectively. Our findings suggest that in vivo, at low doses of LPS (100 μg/mouse), LPS-induced bone resorption is mediated by IL-11 and PGs, while at high doses of LPS (500 μg/mouse), it is mediated by IL-11, PGs, IL-1, and TNF signaling. IL-11 and PGs mediate LPS-induced bone resorption by enhancing osteoclastogenesis independently of the IL-1 or TNF signaling.

scholarly journals POS0400 METABOLIC CHANGES INDUCED BY ANTI-MALONDIALDEHYDE/MALINDIALDEHYDE-ACETALDEHYDE ANTIBODIES PROMOTE OSTEOCLAST DEVELOPMENT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 429-429
Author(s):  
K. Sakuraba ◽  
A. Krishnamurthy ◽  
A. Circiumaru ◽  
V. Joshua ◽  
H. Wähämaa ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Bone Loss ◽  
Molecular Mechanisms ◽  
Cellular Metabolism ◽  
Tca Cycle ◽  
Tartrate Resistant Acid Phosphatase ◽  
Fcγ Receptor ◽  
Research Support

Background:Malondialdehyde (MDA) is a highly reactive compound generated during lipid-peroxidation in conditions associated with oxidative stress. MDA can irreversibly modify proteins (e.g. lysine, arginine and histidine residues). In addition, acetaldehyde can further react with MDA adducts to form malondialdehyde-acetaldehyde (MAA) modification. Such protein modifications can lead to immunogenic neo-epitopes that are recognized by autoantibodies. In fact, anti-MDA/MAA IgG antibodies are significantly increased in the serum of patients with autoimmune diseases, such as rheumatoid arthritis (RA) (1). Interestingly, anti-MDA/MAA antibodies have been shown to promote osteoclast (OC) differentiation in vitro suggesting a potential role for these autoantibodies in bone damage associated with RA (1).Objectives:Little is known about the molecular mechanisms activated by autoantibodies in RA. Here, we elucidate the pathways specifically triggered by anti-MDA/MAA autoantibodies in developing osteoclasts.Methods:Recombinant human monoclonal anti-MDA/MAA antibodies, which were previously cloned from single synovial B cells of RA patients, were added to different OC assays. OCs were generated from monocyte-derived macrophages in the presence of the cytokines RANK-L and M-CSF. OC development was monitored by light microscopy following tartrate-resistant acid phosphatase staining and by erosion assays using calcium phosphate-coated plates. Bone morphometrics were studied in anti-MDA/MAA-injected mice using X-ray microscopy. Cellular metabolism was analyzed by mass spectrometry, Seahorse XF Analyzer and a colorimetric L-Lactate assay.Results:Anti-MDA/MAA antibodies induced a robust OC differentiation in vitro and bone loss in vivo. The anti-MDA/MAA antibodies acted on developing OCs by increasing glycolysis via an Fcγ receptor I-mediated pathway and the upregulation of the transcription factors HIF-1α, Myc and CHREBP. Such regulation of cellular metabolism was exclusively observed in the presence of the osteoclastogenic anti-MDA/MAA clones, whereas other RA-associated autoantibodies (anti-MDA/MAA or anti-citrullinated protein antibodies) had no effect on metabolism. The anti-MDA/MAA treatment induced a shift in the tricarboxylic acid (TCA) cycle activity in developing OCs, leading to the accumulation of citrate and aconitate.Conclusion:We described a novel type of autoantibody-induced pathway in RA, which might contribute to increased OC activation and a consequent bone loss. Anti-MDA/MAA antibodies promoted osteoclast development by increasing glycolysis and by modulating the TCA cycle through a signaling pathway that included Fcγ receptor I and a network of transcription factors acting on glycolysis. A TCA cycle bias towards citrate production suggests that the anti-MDA/MAA antibodies might stimulate OCs via increasing lipid biosynthesis in the cells.References:[1]Grönwall C. et al. J. Autoimmunity 84 (2017): 29-45.Acknowledgements:This Project has received funding from FOREUM, Foundation for Research in Rheumatology, from the European Research Council (ERC) grant agreement CoG 2017 - 7722209_PREVENT RA, the EU/EFPIA Innovative Medicine Initiative grant agreement 777357_RTCure, the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse and Knut and Alice Wallenberg Foundation.Disclosure of Interests:Koji Sakuraba: None declared, Akilan Krishnamurthy: None declared, Alexandra Circiumaru: None declared, Vijay Joshua: None declared, Heidi Wähämaa: None declared, Marianne Engström: None declared, Meng Sun: None declared, Xiaowei Zheng: None declared, Cheng Xu: None declared, Khaled Amara: None declared, Vivianne Malmström Grant/research support from: collaboration with Pfizer, unrelated to the abstract, Sergiu-Bogdan Catrina: None declared, Caroline Grönwall: None declared, Bence Réthi: None declared, Anca Catrina Grant/research support from: collaboration with BMS and Pfizer, unrelated to the present abstract

scholarly journals X-ray-based virtual slicing of TB-infected lungs

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ana Ortega-Gil ◽  
Juan José Vaquero ◽  
Mario Gonzalez-Arjona ◽  
Joaquín Rullas ◽  
Arrate Muñoz-Barrutia
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
3D Visualization ◽  
Post Mortem ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Preclinical Research ◽  
X Ray ◽  
The Right

AbstractHollow organs such as the lungs pose a considerable challenge for post-mortem imaging in preclinical research owing to their extremely low contrast and high structural complexity. The aim of our study was to enhance the contrast of tuberculosis lesions for their stratification by 3D x-ray–based virtual slicing. Organ samples were taken from five control and five tuberculosis-infected mice. Micro-Computed Tomography (CT) scans of the subjects were acquired in vivo (without contrast agent) and post-mortem (with contrast agent). The proposed contrast-enhancing technique consists of x-ray contrast agent uptake (silver nitrate and iodine) by immersion. To create the histology ground-truth, the CT scan of the paraffin block guided the sectioning towards specific planes of interest. The digitalized histological slides reveal the presence, extent, and appearance of the contrast agents in lung structures and organized aggregates of immune cells. These findings correlate with the contrast-enhanced micro-CT slice. The abnormal densities in the lungs due to tuberculosis disease are concentrated in the right tail of the lung intensity histograms. The increase in the width of the right tail (~376%) indicates a contrast enhancement of the details of the abnormal densities. Postmortem contrast agents enhance the x-ray attenuation in tuberculosis lesions to allow 3D visualization by polychromatic x-ray CT, providing an advantageous tool for virtual slicing of whole lungs. The proposed contrast-enhancing technique combined with computational methods and the diverse micro-CT modalities will open the doors to the stratification of lesion types associated with infectious diseases.

scholarly journals Deferoxamine Reduces Inflammation and Osteoclastogenesis in Avulsed Teeth

2021 ◽  
Vol 22 (15) ◽  
pp. 8225
Author(s):  
Ko Eun Lee ◽  
Mijeong Jeon ◽  
Seunghan Mo ◽  
Hyo-Seol Lee ◽  
Je Seon Song ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Alveolar Bone ◽  
Root Surface ◽  
Tartrate Resistant Acid Phosphatase ◽  
Micro Ct ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Model Cell

Replacement and inflammatory resorption are serious complications associated with the delayed replantation of avulsed teeth. In this study, we aimed to assess whether deferoxamine (DFO) can suppress inflammation and osteoclastogenesis in vitro and attenuate inflammation and bone resorption in a replanted rat tooth model. Cell viability and inflammation were evaluated in RAW264.7 cells. Osteoclastogenesis was confirmed by tartrate-resistant acid phosphatase staining, reactive oxygen species (ROS) measurement, and quantitative reverse transcriptase–polymerase chain reaction in teeth exposed to different concentrations of DFO. In vivo, molars of 31 six-week-old male Sprague–Dawley rats were extracted and stored in saline (n = 10) or DFO solution (n = 21) before replantation. Micro-computed tomography (micro-CT) imaging and histological analysis were performed to evaluate inflammation and root and alveolar bone resorption. DFO downregulated the genes related to inflammation and osteoclastogenesis. DFO also reduced ROS production and regulated specific pathways. Furthermore, the results of the micro-CT and histological analyses provided evidence of the decrease in inflammation and hard tissue resorption in the DFO group. Overall, these results suggest that DFO reduces inflammation and osteoclastogenesis in a tooth replantation model, and thus, it has to be further investigated as a root surface treatment option for an avulsed tooth.

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