scholarly journals The Effects of 2-Aminoethoxydiphenyl Borate (2-APB) and Dantrolene on Rat Bones Treated With NaAsO2

Author(s):  
Jia Feng ◽  
Wenjuan Qin ◽  
Hailong Lv ◽  
Zhen Wang ◽  
Zijing Zhai ◽  
...  

Abstract Objective To observe the effects of arsenic and the protective effects of 2-aminoethoxydiphenyl borate (2-APB) and dantrolene on the trabeculae of Sprague Dawley (SD) rats. Methods Thirty-six SD rats were randomly divided into a control group and an arsenic poisoning group. After 12 weeks of arsenic exposure, six rats in the arsenic poisoning group were randomly selected for sacrifice. The remaining rats were randomly assigned to four groups (n=6 per group): natural recovery after arsenic exposure, dantrolene intervention after arsenic exposure, 2-APB intervention after arsenic exposure, and 2-APB + dantrolene intervention after arsenic exposure. After 21 days of treatment by oral gavage every other day, the bilateral femurs and tibias of the rats were scanned using micro-computed tomography (micro-CT). Bone marrow stromal cells (BMSCs) were isolated and cultured, and Ca2+ concentration and alkaline phosphatase (ALP) activity of BMSCs was assessed. Results Compared with the control group, bone mineralization density (BMD), bone volume (BV)-to-total volume (TV) ratio (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and degree of anisotropy (DA) decreased, while trabecular separation (Tb.Sp), trabecular pattern factor (TBpf), and structural model index (SMI) increased in the arsenic poisoning group (P<0.05); additionally, Ca2+ concentration increased and ALP activity decreased significantly in the arsenic poisoning group (P<0.05). Compared with the natural recovery group, after arsenic exposure, the indices of micro-CT recovered to some extent, the Ca2+ concentration of BMSCs decreased significantly, and the ALP activity of BMSCs increased significantly after intervention with 2-APB and dantrolene (P<0.05). Conclusion Arsenic can lead to significant changes in the structure of trabeculae and osteoporosis in rats, and these changes can be improved by intervention with 2-APB and dantrolene.

2019 ◽  
Vol 9 (8) ◽  
pp. 1127-1132 ◽  
Author(s):  
Long Wang ◽  
Jian Yu

BMSCs play an important role in osteoporosis (OP) and their differentiation can lead to OP progression. Mir-149 can participate in the regulation of BMSCs. However, the effect of Mir-149 on BMSCs in osteoporosis remains unclear. SD rats were divided control group and OP group. OP rat BMSCs were transfected with Mir-149 siRNA followed by analysis of Mir-149 expression by real time PCR, cell proliferation by MTT assay, apoptosis by flow cytometry, ERK/MAPK signaling protein expression by western blot, ALP activity, as well as expression of osteogenic genes Runx2 and OC by real time PCR. Mir-149 expression was significantly increased in BMSCs of OP rats, cell proliferation was inhibited, apoptosis was increased, as well as p-ERK1/2 expression, ALP activity and expression of Runx2 and OC was decreased compared to control group (P < 0.05). Transfection of Mir-149 siRNA into OP rat BMSCs reduced Mir-149 expression, promoted cell proliferation, decreased apoptotic rate, increased p-ERK1/2 expression, ALP activity and Runx2 and OC expression. Compared with OP group, the differences were statistically significant (P< 0.05). Mir-149 expression was increased in OP rat BMSCs. Down-regulation of Mir-149 promoted the activation of ERK/MAPK signaling pathway, inhibited apoptosis of BMSCs and promoted the proliferation and osteogenic differentiation of BMSCs in OP rats.


2021 ◽  
Author(s):  
Fan Yu ◽  
Bo Li ◽  
Guoliang Zhang ◽  
Song Zhou

Abstract ObjectiveTo investigate whether interleukin-17 receptor C (il-17rc) gene knockout leads to systemic osteoporosis in transgenic mice. MethodsThe immunohistochemistry and micro computed tomography (micro-CT) were used to analyze the condition of vertebral cancellous bone in 3-month healthy female wild-type C57BL/6 mice (control group) and il-17rc gene knockout C57BL/6 mice (experimental group). ResultsWild type C57BL/6 mice had higher bone density per unit volume (0.52 ± 0.12 vs. 0.47 ± 0.05, P = 0.028) (g/cm3), more trabecular connections (8.97 ± 1.46 vs. 5.59 ± 3.15, P = 0.017) (1/mm), thicker trabecular thickness (0.16 ± 0.08 vs. 0.10 ± 0.04, P = 0.029) (1/mm) and the number of trabeculae was more (5.01 ± 0.33 vs. 3.16 ± 0.37, P = 0.038) (1/mm) than mut-il-17rc mice. In addition, the results of micro-CT also showed that the osteoporosis of il-17rc gene knockout C57BL/6 mice was mainly manifested in T13 (P = 0.039), L1 (P = 0.035), L3 (P = 0.018), L5 (P = 0.021) and L6 (P = 0.036), but the mean bone mineral density between L2 (P = 0.317) and L4 (P = 0.242) was no significant difference between the two groups. ConclusionIL-17/il-17rs signal axis is widely distributed in the animal skeletal system and is one of the important signal pathways regulating bone metabolism. Knockout of il-17rc gene can lead to the occurrence of osteoporosis in model animals.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Joseph Munoz ◽  
Shalom Siebert ◽  
Weimin Guo ◽  
Erin Lewis ◽  
Lijun Li ◽  
...  

Abstract Objectives Osteoporosis is a debilitating disease that increases with age and is characterized by increased bone fragility. However, dietary factors can influence the development of osteoporosis. For example, high fat diets (HFD) have been shown to have detrimental effects on bone density and quantity. However, the effects of HFD on bone microarchitecture have not been extensively studied. The architecture of the bone is important because it provides information regarding the quality of the bone and not just quantity. Therefore, the purpose of this study was to investigate the effects of HFD on bone microarchitecture in mice when compared to low fat diet fed mice. Methods Five-week-old mice were randomized into two different treatment groups, control and HFD (n = 6 per group). The control group were fed AIN-93 G growing rodent diet (20% protein, 65% carbohydrate (CHO), 15% fat) while the HFD group was fed a standard HFD ordered from Research Diets Inc. Cat #D12451M (20% protein, 35% CHO, 45% fat) for 20 weeks. After 20 weeks the animals were sacrificed and left tibial bone specimen were prepared for analysis via micro-computed tomography. Data were analyzed using one-way ANOVA to detect differences between groups. Results Mean values ± SEM for bone measurements (control, HFD) are as follows. Total Volume (TV) (6.04 mm3 ± 0.077, 6.16 mm3 ± 0.12 mm), bone volume (BV) (2.33 mm3 ± 0.054, 1.89 mm3 ± 0.06), BV/TV (0.386% ± 0.011, 0.31% ± 0.01), structural model index (SMI) (−0.687 ± 0.097, −0.35 ± 0.09), connective density (Conn.D) (775.83 ± 51.2, 693.8 ± 91.7), trabecular number (Tb.N) (7.52 mm ± 0.135, 6.23 mm ± 0.32), trabecular thickness (Tb.Th) (0.059 mm ± 0.0009, 0.056 mm ± 0.00069), and trabecular separation (Tb.Sp) (0.139 mm ± 0.003, 0.18 mm ± 0.0063). BV, BV/TV, Tb.N and Tb.Th values were all significantly higher (P < 0.05) in the control group versus the HFD group while SMI and Tb.Sp were significantly lower (P < 0.05). Conclusions These results agree with previous studies showing that HFD has detrimental effects on bone. This study demonstrated that HFD negatively impacts the microarchitecture of bone, specifically trabecular number, thickness, and separation which are important for overall structure, strength, and flexibility of bone. Future studies should focus on mechanisms underlying the role of HFD on the microarchitecture of bone. Funding Sources None


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuyou Qiu ◽  
Cuisong Tang ◽  
Mario Serrano-Sosa ◽  
Jian Hu ◽  
Jingqi Zhu ◽  
...  

Abstract Background This study is aimed to determine the efficacy of X-Ray Microtomography (micro-CT) in predicting oxytocin (OT) treatment response in rabbit osteoporosis(OP) model. Methods Sixty-five rabbits were randomly divided into three groups: control group, ovariectomy (OVX) -vehicle and OVX-oxytocin group. The controls underwent sham surgery. OVX-vehicle and OVX-oxytocin groups were subjected to bilateral OVX. The rabbits in OVX-oxytocin group were injected with oxytocin. In the 0th, 4th, 8th, 10th and 12th weeks post OVX operation, bone mineral density (BMD) and bone micro-architectural parameters were measured in three groups. Results Bone mineral density (BMD), bone volume fraction (BV/TV), Trabecular Number (Tb.N), and Trabecular Thickness (Tb.Th) decreased, while Trabecular Spacing (Tb.Sp) and Structure Model Index (SMI) increased overtime in all the three groups. In OVX-oxytocin group, the bone deterioration tendency is slowing down compared with that of the OVX-vehicle group. The BMD of the OVX-oxytocin group was significantly lower than those in the OVX-vehicle group at 12th week (P = 0.017). BV/TV and Tb.Sp in OVX-oxytocin group changed significantly from 8th week (P = 0.043) and 12th week (P = 0.014), which is earlier than that of BMD and other bone micro-architectural parameters. Conclusion BV/TV and Tb.Sp changed prior to BMD and other bone micro-architectural parameters with oxytocin intervention, which indicate that they are more sensitive markers for predicting early osteoporosis and treatment monitoring when using micro-CT to evaluate osteoporosis rabbit model.


2020 ◽  
Author(s):  
Samantha Maurotti ◽  
Cristina Russo ◽  
Vincenzo Musolino ◽  
Saverio Nucera ◽  
Micaela Gliozzi ◽  
...  

AbstractPathological pathways involved in the development of diabetic complications are still unclear. Several studies suggested a pathogenic role of C-peptide deficiency in vascular and neuropathic complications. However, to date, the role of C-peptide on diabetes-related bone loss has not been investigated. The objective of this study was to test the effects of a 6-week regimen of rat C-peptide infusion on bone by combining micro-CT imaging with histological testing.Twenty-three, four-month-old male Wistar rats were randomly divided into three groups: Normal control group; Sham diabetic control group; Diabetic plus C-peptide group. Diabetes was induced by injection of streptozotocin. Rat C-peptide was delivered via subcutaneously osmopumps. We assessed several trabecular microarchitectural parameters and cellular and matrix proteins in bone tissue sections.At the end of the study, both the normal control and diabetic plus C-peptide groups had a higher tibia weight than the diabetic control group (p = 0.05 and p = 0.02, respectively). C-peptide levels significantly and positively correlated with the trabecular thickness (r= 0.45, p=0.08) and negatively with structure model index (r= −0.40, p=0.09). Furthermore, it positively correlated with one of the histological assessments (i.e. PLIN1 score; p=0.02). Micro-CT evaluation showed significant inter-group differences in trabecular thickness (p=0.02), trabecular space (p = 0.05) and cross-sectional thickness (p=0.05). Diabetic plus C-peptide group showed a higher trabecular thickness (p<0.001), cross-sectional thickness (p=0.03) and a lower trabecular space (p=0.05) than the normal control group. Both the normal control and diabetic plus C-peptide groups had more Runx-2 and PLIN1 positive cells in comparison to the diabetic control group (p = 0.045 and p = 0.034).For the first time we demonstrated that the diabetic rats receiving rat C-peptide had higher quality of trabecular bone, than diabetic rats not receiving it. C-peptide could have a role in the prevention of diabetes-related bone loss.


2021 ◽  
Vol 11 (3) ◽  
pp. 891
Author(s):  
Taylor Flaherty ◽  
Maryam Tamaddon ◽  
Chaozong Liu

Osteochondral scaffold technology has emerged as a promising therapy for repairing osteochondral defects. Recent research suggests that seeding osteochondral scaffolds with bone marrow concentrate (BMC) may enhance tissue regeneration. To examine this hypothesis, this study examined subchondral bone regeneration in scaffolds with and without BMC. Ovine stifle condyle models were used for the in vivo study. Two scaffold systems (8 mm diameter and 10 mm thick) with and without BMC were implanted into the femoral condyle, and the tissues were retrieved after six months. The retrieved femoral condyles (with scaffold in) were examined using micro-computed tomography scans (micro-CT), and the micro-CT data were further analysed by ImageJ with respect to trabecular thickness, bone volume to total volume ratio (BV/TV) ratio, and degree of anisotropy of bone. Statistical analysis compared bone regeneration between scaffold groups and sub-set regions. These results were mostly insignificant (p < 0.05), with the exception of bone volume to total volume ratio when comparing scaffold composition and sub-set region. Additional trends in the data were observed. These results suggest that the scaffold composition and addition of BMC did not significantly affect bone regeneration in osteochondral defects after six months. However, this research provides data which may guide the development of future treatments.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jae-Young Kim ◽  
Hyo-Won Jang ◽  
Jung-In Kim ◽  
In-Ho Cha

AbstractThe purpose of this study was to investigate the effect of administering intermittent parathyroid hormone (iPTH) before tooth extraction versus after tooth extraction on the risk of developing MRONJ in experimental animal model. Twenty-five ovariectomized rats received 6 weeks of bisphosphonate therapy. They were classified into 3 groups, based on the timing of the medication, as Control, Pre-PTH and Post-PTH groups. For Control group, normal saline was administered before and after tooth extraction. iPTH was administered during 4 weeks before tooth extraction for Pre-PTH group and after tooth extraction for Post-PTH group. The animals were euthanized 8 weeks after tooth extraction. Macroscopic, histological, micro-computed tomography (micro-CT), and histomorphometric examinations were conducted. The incidences of impaired healing were 11.11% both in Pre-PTH and Post-PTH groups, which was lower than the Control group (42.86%). Bone healing in the extraction socket, based on micro-CT and histomorphometry evaluations, was best in Post-PTH and worst in Control group. The Pre-PTH group showed moderate healing pattern. Despite of limitations in this study, the authors identified Pre-PTH group seems to have positive effect on extraction socket healing. With regard to timing, administering iPTH after tooth extraction was superior to applying it before tooth extraction.


2018 ◽  
Vol 17 (3) ◽  
pp. 806-812 ◽  
Author(s):  
Tao Wu ◽  
Aiqin Zhang ◽  
Hongyang Lu ◽  
Qiaoyuan Cheng

Background: The blood-brain barrier (BBB) is the greatest challenge in the treatment of intracranial malignant tumors. Objective: The aim of this study is to determine the role of borneol in opening the BBB and elucidate the underlying mechanisms. Materials and Methods: Twenty Sprague-Dawley (SD) rats were randomized into borneol group intragastrically administered with 10% borneol corn oil (2 mL/kg) and control group. After 30 minutes, 2% Evans blue (4 mL/kg) was injected. Thirty minutes later, brain tissue was analyzed using the Evans blue standard curve. Another 40 SD rats were randomized into high-, medium-, and low-dose borneol groups and a control group. Each rat in the experimental groups was intragastrically administered with 10% borneol corn oil (2 mL/kg, 1.25 mL/kg, and 0.5 mL/kg, respectively). The control group was injected with corn oil of 1.25 mL/kg. After 30 minutes, the rats were killed, and the brain tissues were collected. The expression of occludin, occludens-1, nitric oxide synthase, P-glycoprotein, and intercellular cell adhesion molecule-1 (ICAM-1) was detected by immunohistochemy. Results: The concentration of Evans blue in the borneol group was higher than in the control group ( P < .05). The mean density of ICAM-1 expression was higher in the experimental group than in the control group ( P < .05). In contrast, significant differences of positive area and total density of ICAM-1 were shown only between the high-dose group and the control group ( P < .05). Conclusion: Borneol can open the BBB, which might be related with the increased expression of ICAM-1.


2006 ◽  
Vol 321-323 ◽  
pp. 1070-1073
Author(s):  
Ye Yeon Won ◽  
Myong Hyun Baek ◽  
Wen Quan Cui ◽  
Kwang Kyun Kim

This study investigates micro-structural and mechanical properties of trabecular bone in human femoral head with and without osteoporosis using a micro-CT and a finite element model. 15 cored trabecular bone specimens with 20 of diameter were obtained from femoral heads with osteoporosis resected for total hip arthroplasty, and 5 specimens were removed from femoral head of cadavers, which has no history of musculoskeletal diseases. A high-resolution micro-CT system was used to scan each specimen to obtain histomorphometry indexes. Based on the micro-images, a FE-model was created to determine mechanical property indexes. While the non-osteoporosis group had increases the trabecular thickness, the bone volume, the bone volume fraction, the degree of anisotropy and the trabecular number compared with those of osteoporotic group, the non-osteoporotic group showed decreases in trabecular separation and structure model index. Regarding the mechanical property indexes, the reaction force and the Young's modulus were lower in the osteoporotic group than in non-osteoporotic group. Our data shows salient deteriorations in trabecular micro-structural and mechanical properties in human femoral head with osteoporosis.


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