scholarly journals Technetium-99 Conjugated with Methylene Diphosphonate Ameliorates Glucocorticoid Induced Osteoporosis by Inhibiting Osteoclastogenesis

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Lianjie Shi ◽  
Ying Ning ◽  
Liling Xu ◽  
Jianhong Li ◽  
Xuewu Zhang

Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) is an effective anti-inflammatory drug in treating rheumatoid arthritis (RA) for over 15 years in China. However, as a special form of bisphosphonate, the antiosteoporotic effect of99Tc-MDP is unclear. We systematically investigated the effects of99Tc-MDP on cancellous and cortical bone, respectively, in glucocorticoid induced osteoporosis (GIO) animal models. Forty-eight Sprague-Dawley rats were randomly divided into six groups: blank, negative control, high dose, medium dose, low dose, and positive control groups. After dexamethasone was given to all groups except the blank group to induce osteoporosis, the rats in different groups were treated with saline, MDP, or different doses of99Tc-MDP. After treatment, all rats were sacrificed, and their tibiae and femora were analyzed with microcomputed tomography (micro-CT), histology and biomechanics. Micro-CT analyses showed that (1)99Tc-MDP reversed glucocorticoid induced bone microarchitecture destruction by increasing BV/TV, Tb.Th, and Tb.N and decreasing BS/BV, Tb.Sp, and TBPf; (2) effect of99Tc-MDP increased as its dosage increased; and (3)99Tc-MDP could improve cortical bone thickness while MDP failed to do so. Micro-CT spatial structure analysis and histology also yielded consistent results, indicating that99Tc-MDP increased trabecular number and connectivity morphologically. Secondly, biomechanics revealed that99Tc-MDP can enhance the extrinsic stiffness of bone by changing bone geometry. Finally,99Tc-MDP could inhibit osteoclastogenesis in PBMCs in human. In conclusion,99Tc-MDP exerted antiosteoporotic effect by improving both cancellous and cortical bone, as well as increasing extrinsic bone stiffness which might be attributed to the its inhibition of osteoclast differentiation. The antiosteoporotic effect of99Tc-MDP may suggest a potential clinical application for patients with GIO.

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Rosmaliza Ramli ◽  
Mohd Fadhli Khamis ◽  
Ahmad Nazrun Shuid

Recent studies suggested thatEurycoma longifolia, a herbal plant, may have the potential to treat osteoporosis in elderly male. This study aimed to determine the effects ofEurycoma longifoliasupplementation on the trabecular bone microarchitecture of orchidectomised rats (androgen-deficient osteoporosis model). Forty-eight-aged (10–12 months old)Sprague Dawleyrats were divided into six groups of sham-operated (SHAM), orchidectomised control (ORX), orchidectomised + 7 mg/rat testosterone enanthate (TEN) and orchidectomised +Eurycoma longifolia30 mg/kg (EL30), orchidectomised +Eurycoma longifolia60 mg/kg (EL60), orchidectomised +Eurycoma longifolia90 mg/kg (EL90). Rats were euthanized following six weeks of treatment. The left femora were used to measure the trabecular bone microarchitecture using micro-CT. Orchidectomy significantly decreased connectivity density, trabecular bone volume, and trabecular number compared to the SHAM group. Testosterone replacement reversed all the orchidectomy-induced changes in the micro-CT parameters. EL at 30 and 60 mg/kg rat worsened the trabecular bone connectivity density and trabecular separation parameters of orchidectomised rats. EL at 90 mg/kg rat preserved the bone volume. High dose of EL (90 mg/kg) may have potential in preserving the bone microarchitecture of orchidectomised rats, but lower doses may further worsen the osteoporotic changes.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Zhixing Jin ◽  
Li Wang ◽  
Zhiling Zhu

Objective. To evaluate the effect of GuiXiong Xiaoyi Wan (GXXYW) on the development of endometriosis in a rat model.Methods. Sprague-Dawley rats with surgically induced endometriosis were randomly treated with low-dose GXXYW, high-dose GXXYW, or vehicle (negative control) for 28 days. Immunohistochemistry was used to assess cell proliferation in the lesions. The terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP biotin nick end labelling (TUNEL) method was performed to analyse the apoptosis induced by GuiXiong Xiaoyi Wan. The percentages of CD3+ lymphocytes, CD4+ lymphocytes, and CD8+ lymphocytes in the spleens of the rats were evaluated using flow cytometric analysis.Results. Treatment with GXXYW significantly decreased the lesion size, inhibited cell proliferation, and induced apoptosis in endometriotic tissue. The spleens of GXXYW-treated rats also demonstrated a significant increase in the percentage of CD4+ lymphocytes and a significant decrease in the percentage of CD8+ lymphocytes.Conclusions. These results suggest that, in a rat model, GXXYW may be effective in the suppression of the growth of endometriosis, possibly through the inhibition of cell proliferation, the induction of apoptosis of endometriotic cells, and the regulation of the immune system.


PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e107545 ◽  
Author(s):  
Jui-Ting Hsu ◽  
Ying-Ju Chen ◽  
Jung-Ting Ho ◽  
Heng-Li Huang ◽  
Shun-Ping Wang ◽  
...  

2018 ◽  
Vol 24 (13) ◽  
pp. 1395-1404
Author(s):  
Elham Bagheri ◽  
Kamelia Saremi ◽  
Fatemeh Hajiaghaalipour ◽  
Fadhil Lafta Faraj ◽  
Hapipah Mohd Ali ◽  
...  

Quinazoline is an aromatic bicyclic compound exhibiting several pharmaceutical and biological activities. This study was conducted to investigate the potential wound healing properties of Synthetic Quinazoline Compound (SQC) on experimental rats. The toxicity of SQC was determined by MTT cell proliferation assay. The healing effect of SQC was assessed by in vitro wound healing scratch assay on the skin fibroblast cells (BJ-5ta) and in vivo wound healing experiment of low and high dose of SQC on adult Sprague-Dawley rats compared with negative (gum acacia) and positive control (Intrasite-gel). Hematoxylin and Eosin (H&E), Masson’s Trichrome (MT) staining and immunohistochemistry analysis were performed to evaluate the histopathological alterations and proteins expression of Bax and Hsp70 on the wound tissue after 10 days. In addition, levels of antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase), and malondialdehyde (MDA) were measured in wound tissue homogenates. The SQC significantly enhanced BJ-5ta cell proliferation and accelerated the percentage of wound closure, with less scarring, increased fibroblast and collagen fibers and less inflammatory cells compared with the negative control. The compound also increases endogenous enzymes and decline lipid peroxidation in wound homogenate.


2012 ◽  
Vol 112 (5) ◽  
pp. 918-925 ◽  
Author(s):  
B. R. Macias ◽  
J. M. Swift ◽  
M. I. Nilsson ◽  
H. A. Hogan ◽  
S. D. Bouse ◽  
...  

Mechanical loading modulates the osteocyte-derived protein sclerostin, a potent inhibitor of bone formation. We hypothesized that simulated resistance training (SRT), combined with alendronate (ALEN) treatment, during hindlimb unloading (HU) would most effectively mitigate disuse-induced decrements in cortical bone geometry and formation rate (BFR). Sixty male, Sprague-Dawley rats (6-mo-old) were randomly assigned to either cage control (CC), HU, HU plus either ALEN (HU+ALEN), or SRT (HU+SRT), or combined ALEN and SRT (HU+SRT/ALEN) for 28 days. Computed tomography scans on days − 1 and 28 were taken at the middiaphyseal tibia. HU+SRT and HU+SRT/ALEN rats were subjected to muscle contractions once every 3 days during HU (4 sets of 5 repetitions; 1,000 ms isometric + 1,000 ms eccentric). The HU+ALEN and HU+SRT/ALEN rats received 10 μg/kg ALEN 3 times/wk. Compared with the CC animals, HU suppressed the normal slow growth-induced increases of cortical bone mineral content, cortical bone area, and polar cross-sectional moment of inertia; however, SRT during HU restored cortical bone growth. HU suppressed middiaphyseal tibia periosteal BFR by 56% vs. CC ( P < 0.05). However, SRT during HU restored BFR at both periosteal (to 2.6-fold higher than CC) and endocortical (14-fold higher than CC) surfaces ( P < 0.01). ALEN attenuated the SRT-induced BFR gains during HU. The proportion of sclerostin-positive osteocytes in cortical bone was significantly higher (+121% vs. CC) in the HU group; SRT during HU effectively suppressed the higher proportion of sclerostin-positive osteocytes. In conclusion, a minimum number of high-intensity muscle contractions, performed during disuse, restores cortical BFR and suppress unloading-induced increases in sclerostin-positive osteocytes.


2018 ◽  
Vol 47 (6) ◽  
pp. 376-384 ◽  
Author(s):  
Ashish K. Sharma ◽  
Nigel D. Toussaint ◽  
Rosemary Masterson ◽  
Stephen G. Holt ◽  
Chamith S. Rajapakse ◽  
...  

Background: Cortical bone is a significant determinant of bone strength and its deterioration contributes to bone fragility. Thin cortices and increased cortical porosity have been noted in patients with chronic kidney disease (CKD), but the “Turnover Mineralization Volume” classification of renal osteodystrophy does not emphasize cortical bone as a key parameter. We aimed to assess trabecular and cortical bone microarchitecture by histomorphometry and micro-CT in patients with CKD G5 and 5D (dialysis). Methods: Transiliac bone biopsies were performed in 14 patients undergoing kidney transplantation (n = 12) and parathyroidectomy (n = 2). Structural parameters were analysed by histomorphometry and micro-CT including trabecular bone volume, thickness (TbTh), number (TbN) and separation and cortical thickness (CtTh) and porosity (CtPo). Indices of bone remodelling and mineralisation were obtained and relationships to bone biomarkers examined. Associations were determined by Spearman’s or Pearson’s rank correlation coefficients. Results: By micro-CT, trabecular parameters were within normal ranges in most patients, but all patients showed very low CtTh (127 ± 44 µm) and high CtPo (60.3 ± 22.5%). CtPo was inversely related to TbN (r = –0.56; p = 0.03) by micro-CT and to TbTh (r = –0.60; p = 0.024) by histomorphometry and correlated to parathyroid hormone values (r = 0.62; p = 0.021). By histomorphometry, bone turnover was high in 50%, low in 21% and normal in 29%, while 36% showed abnormal patterns of mineralization. Significant positive associations were observed between osteoblast surface, osteoclast surface, mineralization surface and bone turnover markers. Conclusions: Deterioration of cortical ­microarchitecture despite predominantly normal trabecular parameters reinforces the importance of comprehensive cortical evaluation in patients with CKD.


Bone ◽  
2006 ◽  
Vol 38 (1) ◽  
pp. 136-144 ◽  
Author(s):  
Cedo M. Bagi ◽  
Nels Hanson ◽  
Catharine Andresen ◽  
Richard Pero ◽  
Roland Lariviere ◽  
...  

2021 ◽  
Vol 18 (9) ◽  
pp. 1845-1851
Author(s):  
Xiaona Ma ◽  
Yanhui Wu ◽  
Bingbing Li ◽  
Zheng Wang ◽  
Xiujuan Zhu ◽  
...  

Purpose: To explore the therapeutic role of amber powder in endometriosis by investigating its effect on endometrial ultrastructure, ERK1/2, p38MAPK, and NF-κB mRNA pathways and CSRC/EFR/ERK1/2 proteins. Methods: Sprague Dawley (SD) rats were randomly divided into blank group, disease model group (untreated), amber powder high-dose group, amber powder medium-dose group, amber powder lowdose group and danazol group. Morphological changes in endometrial cells were studied using transmission electron microscopy. The expression of ERK1/2, p38MAPK, and NF-κB mRNA in endometrial tissues of each group was determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry was utilized for the measurement of C-SRC/EFR/ERK1/2 pathway protein expression. Results: The endometriosis rats treated with a high-, medium- and low-dose amber powder showed a decrease in the volume of ectopic lesions, compared with the untreated disease model group. The expressions of ERK1/2, p38MAPK, NF-κB mRNA, and C-SRC/EFR/ERK1/2 protein were higher in the eutopic and ectopic endometrial tissues in untreated disease group than those in normal control group. Moreover, treatment of endometriosis rats with amber powder revealed a reduction in the expressions of ERK1/2, p38MAPK, NF-κB mRNA and C-SRC/EFR/ERK1/2 proteins in eutopic and ectopic endometrium tissues. Conclusion: Amber powder reduces ectopic lesions and slows down the development of endometriosis, probably via inhibition of MAPK pathway genes in eutopic and ectopic endometrial tissues.


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