Deferoxamine Reduces Inflammation and Osteoclastogenesis in Avulsed Teeth

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

Antioxidants ◽

10.3390/antiox10040619 ◽

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.

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1,25-Dihydroxy-19-nor-vitamin D2, a Vitamin D Analog with Reduced Bone Resorbing Activity In Vitro

Journal of the American Society of Nephrology ◽

10.1681/asn.v11101857 ◽

2000 ◽

Vol 11 (10) ◽

pp. 1857-1864

Author(s):

L. SHANNON HOLLIDAY ◽

STEPHEN L. GLUCK ◽

EDUARDO SLATOPOLSKY ◽

ALEX J. BROWN

Keyword(s):

Vitamin D ◽

Acid Phosphatase ◽

Bone Resorption ◽

Vitamin D Receptor ◽

Intrinsic Activity ◽

Tartrate Resistant Acid Phosphatase ◽

Mouse Bone Marrow ◽

Bone Resorbing Activity

Abstract. 1,25-Dihydroxy-19-nor-vitamin D2 (19-norD2), a new analog of 1,25(OH)2D3, suppresses parathyroid hormone in renal failure patients and in uremic rats but has less calcemic activity than 1,25(OH)2D3. Although 19-norD2 has high affinity for the vitamin D receptor and similar pharmacokinetics to those of 1,25(OH)2D3, it has much less bone resorbing activity in vivo. The intrinsic activity of 19-norD2 on osteoclastogenesis and activation of bone resorption in mouse bone marrow cultures was examined to determine the mechanism involved. 19-norD2 and 1,25(OH)2D3 (10 nM) were equivalent in stimulating the formation and maintenance of large multinucleated, tartrate-resistant acid phosphatase-positive cells. However, the amount of bone resorbed by osteoclasts stimulated by 10 nM 19-norD2, as measured by pit-forming assays, was reduced 62% compared with 10 nM 1,25(OH)2D3-stimulated osteoclasts (P < 0.05). This difference could not be attributed to enhanced catabolism or to downregulated vitamin D receptor. The rate of degradation of 19-norD2 in cultures was approximately 20% greater than 1,25(OH)2D3, not enough to account for the different effects on bone resorption. The VDR levels were identical in cultures that were treated with 19-norD2 and 1,25(OH)2D3. In summary, 19-norD2 is less effective than 1,25(OH)2D3 in stimulating mouse marrow osteoclasts to resorb bone. The reason for this difference is not clear but seems to involve the late maturation and/or activation of osteoclasts as the number of pits produced by each tartrate-resistant acid phosphatase-positive cell is reduced under stimulation by 19-norD2 compared with 1,25(OH)2D3.

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Radiographic and Micro—Computed Tomographic Imaging of Lipopolysaccharide-Mediated Bone Resorption

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348940911800512 ◽

2009 ◽

Vol 118 (5) ◽

pp. 391-396 ◽

Cited By ~ 5

Author(s):

Robert Nason ◽

Dong H. Lee ◽

Jae Y. Jung ◽

Richard A. Chole

Keyword(s):

Bone Resorption ◽

Chronic Otitis Media ◽

Plain Radiography ◽

Micro Ct ◽

Micro Computed Tomography ◽

Gram Negative ◽

Successful Model ◽

Computed Tomographic ◽

Myeloid Differentiation Factor

Objectives: Chronic otitis media and cholesteatomas cause hearing loss as a result of bony erosion. This bone resorption is known to be more aggressive when cholesteatomas become infected. The most common organism isolated from both diseases is the gram-negative bacterium Pseudomonas aeruginosa. Lipopolysaccharide (LPS), a major virulence factor found in the gram-negative bacterial cell wall, is well known to incite inflammatory bone resorption. The mechanisms underlying this process, however, are poorly understood. In this study, we developed a mouse model of calvarial osteolysis in which resorption was reliably imaged by plain radiography and micro–computed tomography (micro-CT). Methods: A murine calvarial model was developed to study bone resorption induced by P aeruginosa LPS. Calvariae from wild-type and knockout mice used in this model were imaged by plain radiography and micro-CT. Results: A high degree of correlation between plain radiography and micro-CT was identified (R2 = 0.8554). Furthermore, maximal LPS-induced bone resorption required functioning toll-like receptor (TLR) 2, TLR4, and myeloid differentiation factor 88 (MyD88). Conclusions: We have developed a successful model of inflammatory osteolysis in which plain radiography can reliably delineate induced bone resorption. In vivo, we have shown that P aeruginosa LPS signals via TLR2, as well as TLR4 through MyD88.

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Effects of Gold Nanoparticles Combined Human β-defensin 3 on The Alveolar Bone of Experimental Periodontitis

10.21203/rs.3.rs-394810/v1 ◽

2021 ◽

Author(s):

Jing Zhou ◽

Lingjun Li ◽

Di Cui ◽

Xiaoting Xie ◽

Wenrong Yang ◽

...

Keyword(s):

Gold Nanoparticles ◽

Bone Resorption ◽

Alveolar Bone ◽

Ct Scanning ◽

Enzyme Linked Immunosorbent Assay ◽

Tartrate Resistant Acid Phosphatase ◽

Micro Ct ◽

Tnf Α ◽

Experimental Periodontitis ◽

Masson Staining

Abstract Background Nanomaterials of biomedicine and tissue engineering have been proposed in the treatment of periodontitis recently. This study aimed to investigate the effect of gold nanoparticles (AuNPs) combined human β-defensin 3 (hBD3) on the repair of alveolar bone of experimental periodontitis in rats. Methods A model of experimental periodontitis was established by ligating of the maxillary second molars with silk thread in rats, which were treated with or without AuNPs combined hBD3. Micro-focus computerized tomography (micro-CT) scanning, enzyme-linked immunosorbent assay (ELISA) and histological and immunohistochemical staining, including alkaline phosphatase (ALP), osteoprotegerin (OPG) tartrate-resistant acid phosphatase (TRAP) and receptor activator of NF-κB Ligand (RANKL), were used to analyze. Results Micro-CT demonstrated that the alveolar bone resorption was significantly reduced after the treatment of AuNPs combined hBD3. Levels of TNF-α and IL-6 decreased markedly compared with the ligation group. HE and Masson staining showed that AuNPs combined hBD3 group had less inflammatory cell infiltration, collagen fibrosis and fracture, but higher calcification in the new bone tissue. Moreover, the administration of AuNPs combined hBD3 increased the expression of ALP and OPG (related to bone formation) expression, while decreased TRAP and RANKL (related to bone resorption) expression. Conclusions AuNPs combined hBD3 had a protective effect on the progress of experimental periodontitis in rats, and also played a certain role in promoting osteogenesis.

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PEG-modified gadolinium nanoparticles as contrast agents for in vivo micro-CT

Scientific Reports ◽

10.1038/s41598-021-95716-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Charmainne Cruje ◽

P. Joy Dunmore-Buyze ◽

Eric Grolman ◽

David W. Holdsworth ◽

Elizabeth R. Gillies ◽

...

Keyword(s):

Contrast Agent ◽

Contrast Agents ◽

Soft Tissues ◽

Three Dimensional ◽

Blood Pool ◽

Micro Ct ◽

Micro Computed Tomography ◽

Poly Ethylene

AbstractVascular research is largely performed in rodents with the goal of developing treatments for human disease. Micro-computed tomography (micro-CT) provides non-destructive three-dimensional imaging that can be used to study the vasculature of rodents. However, to distinguish vasculature from other soft tissues, long-circulating contrast agents are required. In this study, we demonstrated that poly(ethylene glycol) (PEG)-coated gadolinium nanoparticles can be used as a vascular contrast agent in micro-CT. The coated particles could be lyophilized and then redispersed in an aqueous solution to achieve 100 mg/mL of gadolinium. After an intravenous injection of the contrast agent into mice, micro-CT scans showed blood pool contrast enhancements of at least 200 HU for 30 min. Imaging and quantitative analysis of gadolinium in tissues showed the presence of contrast agent in clearance organs including the liver and spleen and very low amounts in other organs. In vitro cell culture experiments, subcutaneous injections, and analysis of mouse body weight suggested that the agents exhibited low toxicity. Histological analysis of tissues 5 days after injection of the contrast agent showed cytotoxicity in the spleen, but no abnormalities were observed in the liver, lungs, kidneys, and bladder.

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The Characteristics of Vascular Growth in VX2 Tumor Measured by MRI and Micro-CT

Journal of Oncology ◽

10.1155/2012/362096 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

X.-L. Qi ◽

J. Liu ◽

P. N. Burns ◽

G. A. Wright

Keyword(s):

Volume Fraction ◽

Tumor Model ◽

Response To Therapy ◽

Micro Ct ◽

Micro Computed Tomography ◽

Tumor Vascularity ◽

Vx2 Tumor ◽

Relative Blood Volume

Blood supply is crucial for rapid growth of a malignant tumor; medical imaging can play an important role in evaluating the vascular characterstics of tumors. Magnetic resonance imaging (MRI) and micro-computed tomography (CT) are able to detect tumors and measure blood volumes of microcirculation in tissue. In this study, we used MR imaging and micro-CT to assess the microcirculation in a VX2 tumor model in rabbits. MRI characterization was performed using the intravascular contrast agent Clariscan (NC100150-Injection); micro-CT with Microfil was used to directly depict blood vessels with diameters as low as 17 um in tissue. Relative blood volume fraction (rBVF) in the tumor rim and blood vessel density (rBVD) over the whole tumor was calculated using the two imaging methods. Our study indicates that rBVF is negatively related to the volume of the tumor measured by ultrasound (R=0.90). rBVF in the tissue of a VX2 tumor measured by MRIin vivowas qualitatively consistent with the rBVD demonstrated by micro-CTin vitro(R=0.97). The good correlation between the two methods indicates that MRI studies are potentially valuable for assessing characteristics or tumor vascularity and for assessing response to therapy noninvasively.

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OCLI-023, a Novel Pyrimidine Compound, Suppresses Osteoclastogenesis In Vitro and Alveolar Bone Resorption In Vivo

PLoS ONE ◽

10.1371/journal.pone.0170159 ◽

2017 ◽

Vol 12 (1) ◽

pp. e0170159 ◽

Cited By ~ 11

Author(s):

Hye Jung Ihn ◽

Taeho Lee ◽

Ju Ang Kim ◽

Doohyun Lee ◽

Nam Doo Kim ◽

...

Keyword(s):

Bone Resorption ◽

Alveolar Bone

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Structural Dissection andIn VivoEffectiveness of a Peptide Inhibitor ofPorphyromonas gingivalisAdherence toStreptococcus gordonii

Infection and Immunity ◽

10.1128/iai.00361-10 ◽

2010 ◽

Vol 79 (1) ◽

pp. 67-74 ◽

Cited By ~ 73

Author(s):

Carlo Amorin Daep ◽

Elizabeth A. Novak ◽

Richard J. Lamont ◽

Donald R. Demuth

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Alveolar Bone ◽

Alveolar Bone Loss ◽

Peptide Inhibitor ◽

Dental Biofilm ◽

Streptococcal Antigen ◽

Α Helix

ABSTRACTThe interaction of the minor fimbrial antigen (Mfa) with streptococcal antigen I/II (e.g., SspB) facilitates colonization of the dental biofilm byPorphyromonas gingivalis.We previously showed that a 27-mer peptide derived from SspB (designated BAR) resembles the nuclear receptor (NR) box protein-protein interacting domain and potently inhibits this interactionin vitro. Here, we show that the EXXP motif upstream of the NR core α-helix contributes to the Mfa-SspB interaction and that BAR reducesP. gingivaliscolonization and alveolar bone lossin vivoin a murine model of periodontitis. Substitution of Gln for Pro1171or Glu1168increased the α-helicity of BAR and reduced its inhibitory activityin vitroby 10-fold and 2-fold, respectively. To determine if BAR preventsP. gingivalisinfectionin vivo, mice were first infected withStreptococcus gordoniiand then challenged withP. gingivalisin the absence and presence of BAR. Animals that were infected with either 109CFU ofS. gordoniiDL-1 or 107CFU ofP. gingivalis33277 did not show a statistically significant increase in alveolar bone resorption over sham-infected controls. However, infection with 109CFU ofS. gordoniifollowed by 107CFU ofP. gingivalisinduced significantly greater bone loss (P< 0.01) than sham infection or infection of mice with either organism alone.S. gordonii-infected mice that were subsequently challenged with 107CFU ofP. gingivalisin the presence of BAR exhibited levels of bone resorption similar to those of sham-infected animals. Together, these results indicate that both EXXP and the NR box are important for the Mfa-SspB interaction and that BAR peptide represents a potential therapeutic that may limit colonization of the oral cavity byP. gingivalis.

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Strontium Incorporated Coralline Hydroxyapatite for Engineering Bone

ISRN Biomaterials ◽

10.5402/2013/649163 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Waiching Liu ◽

Ting Wang ◽

Yuhui Shen ◽

Haobo Pan ◽

Songlin Peng ◽

...

Keyword(s):

Bone Resorption ◽

Rat Model ◽

Bone Growth ◽

Micro Ct ◽

Coralline Hydroxyapatite ◽

Ct Analysis ◽

Surface Morphologies ◽

Volume Retention

Goniopora was hydrothermally converted to coralline hydroxyapatite (CHA) and incorporated with Sr (Sr-CHA). The pore size of Goniopora was in the range of 40–300 μm with a porosity of about 68%. Surface morphologies of the coral were modified to flake-like hydroxyapatite structures on CHA and the addition of Sr detected on Sr-CHA as confirmed by SEM and EDX. As the first report of incorporating Sr into coral, about 6%–14% Sr was detected on Sr-CHA. The compressive strengths of CHA and Sr-CHA were not compromised due to the hydrothermal treatments. Sr-CHA was studied in vitro using MC3T3-E1 cells and in vivo with an ovariectomized rat model. The proliferation of MC3T3-E1 cells was significantly promoted by Sr-CHA as compared to CHA. Moreover, higher scaffold volume retention (+40%) was reported on the micro-CT analysis of the Sr-CHA scaffold. The results suggest that the incorporation of Sr in CHA can further enhance the osteoconductivity and osteoinductivity of corals. Strontium has been suggested to stimulate bone growth and inhibit bone resorption. In this study, we have successfully incorporated Sr into CHA with the natural porous structure remained and explored the idea of Sr-CHA as a potential scaffolding material for bone regeneration.

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A Novel Method to Quantify Longitudinal Orthodontic Bone Changes with In Vivo Micro-CT Data

Journal of Healthcare Engineering ◽

10.1155/2018/1651097 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8

Author(s):

Chao Wang ◽

Li Cao ◽

Chongshi Yang ◽

Yubo Fan

Keyword(s):

Alveolar Bone ◽

Tooth Movement ◽

Orthodontic Tooth Movement ◽

Bone Modeling ◽

Micro Ct ◽

Sprague Dawley ◽

Mineral Density ◽

Bone Changes ◽

Novel Method

Orthodontic tooth movement (OTM) is the result of region-specific bone modeling under a load. Quantification of this change in the alveolar bone around a tooth is a basic requirement to understand the mechanism of orthodontics. The purpose of this study was to quantify subregional alveolar bone changes during orthodontic tooth movement with a novel method. In this study, 12 Sprague-Dawley (SD) rats were used as an orthodontic model, and one side of the first upper molar was used to simulate OTM. The alveolar bone around the mesial root was reconstructed from in vivo micro-CT images and separated from other parts of the alveolar bone with two semicylinder filters. The amount and rate of OTM, bone mineral density (BMD), and bone volume (BV) around the root were calculated and compared at 5 time points. The results showed that the amount of tooth movement, BMD, and BV can be evaluated dynamically with this method. The molar moved fastest during the first 3 days, and the rate decreased after day 14. BMD decreased from day 0 to day 14 and returned from day 14 to day 28. BV deceased from day 0 to day 7 and from day 14 to day 28. The method created in this study can be used to accurately quantify dynamic alveolar bone changes during OTM.

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