scholarly journals Atorvastatin Promotes Bone Formation in Aged apoE–/– Mice through the Sirt1–Runx2 Axis

2020 ◽  
Author(s):  
Wei Hong ◽  
Zhanying Wei ◽  
Zhaohui Qiu ◽  
Zheng Li ◽  
Chensheng Fu ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Western Blot ◽  
Bone Microarchitecture ◽  
In Vitro Study ◽  
Control Group ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Resorption Marker ◽  
Related Transcription Factor

Abstract Background Statins are the most widely used drugs in elderly patients, the most common clinical application of statins is in aged hyperlipemia patients. There are few studies on the effects and mechanisms of statins on bone in elderly mice with hyperlipemia. The study is to examine the effects of atorvastatin on bone phenotypes and metabolism in aged apolipoprotein E-deficient (apoE –/– ) mice, and the possible mechanisms involved in these changes. Methods Twenty-four 60-week-old apoE –/– mice were randomly allocated to two groups. Twelve mice were orally gavaged with atorvastatin (10 mg/kg body weight/day) for 12 weeks; the others served as the control group. Bone mass and skeletal microarchitecture were determined using micro-CT. Bone metabolism was assessed by serum analyses, qRT-PCR, and Western blot. Bone marrow-derived mesenchymal stem cells (BMSCs) from apoE –/– mice were differentiated into osteoblasts and treated with atorvastatin and Sirt1 inhibitor EX-527. Results The results showed that long-term administration of atorvastatin increases bone mass and improves bone microarchitecture in trabecular bone but not in cortical bone. Furthermore, the serum bone formation marker osteocalcin (OCN) was ameliorated by atorvastatin, whereas the bone resorption marker tartrate-resistant acid phosphatase 5b (Trap5b) did not appear to be impacted by atorvastatin treatment. The mRNA expression of Sirt1, runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and OCN in bone tissue were increased after atorvastatin administration. Western blot showed same trend in Sirt1 and Runx2. The in vitro study showed that when BMSCs from apoE –/– mice were pretreated with EX527, the higher expression of Runx2, ALP and OCN activated by atorvastatin decreased significantly or showed no difference compared with the control. The protein expression of Runx2 showed same trend. Conclusions Accordingly, the current study validates the hypothesis that atorvastatin can increase bone mass and promote osteogenesis in aged apoE −/− mice by regulating the Sirt1–Runx2 axis.

scholarly journals Atorvastatin Promotes Bone Formation in Aged apoE–/– Mice through the Sirt1–Runx2 Axis

2020 ◽  
Author(s):  
Wei Hong ◽  
Zhanying Wei ◽  
Zhaohui Qiu ◽  
Zheng Li ◽  
Chensheng Fu ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Western Blot ◽  
Bone Microarchitecture ◽  
In Vitro Study ◽  
Control Group ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Resorption Marker ◽  
Related Transcription Factor

Abstract Background: Statins are the most widely used drugs in elderly patients, the most common clinical application of statins is in aged hyperlipemia patients. There are few studies on the effects and mechanisms of statins on bone in elderly mice with hyperlipemia. The study is to examine the effects of atorvastatin on bone phenotypes and metabolism in aged apolipoprotein E-deficient (apoE–/–) mice, and the possible mechanisms involved in these changes. Methods: Twenty-four 60-week-old apoE–/– mice were randomly allocated to two groups. Twelve mice were orally gavaged with atorvastatin (10 mg/kg body weight/day) for 12 weeks; the others served as the control group. Bone mass and skeletal microarchitecture were determined using micro-CT. Bone metabolism was assessed by serum analyses, qRT-PCR, and Western blot. Bone marrow-derived mesenchymal stem cells (BMSCs) from apoE–/– mice were differentiated into osteoblasts and treated with atorvastatin and Sirt1 inhibitor EX-527. Results: The results showed that long-term administration of atorvastatin increases bone mass and improves bone microarchitecture in trabecular bone but not in cortical bone. Furthermore, the serum bone formation marker osteocalcin (OCN) was ameliorated by atorvastatin, whereas the bone resorption marker tartrate-resistant acid phosphatase 5b (Trap5b) did not appear obviously changes after the treatment of atorvastatin. The mRNA expression of Sirt1, runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and OCN in bone tissue were increased after atorvastatin administration. Western blot showed same trend in Sirt1 and Runx2. The in vitro study showed that when BMSCs from apoE–/– mice were pretreated with EX527, the higher expression of Runx2, ALP and OCN activated by atorvastatin decreased significantly or showed no difference compared with the control. The protein expression of Runx2 showed same trend. Conclusions: Accordingly, the current study validates the hypothesis that atorvastatin can increase bone mass and promote osteogenesis in aged apoE−/− mice by regulating the Sirt1–Runx2 axis.

scholarly journals Atorvastatin Promotes Bone Formation in Aged apoE–/– Mice through the Sirt1–Runx2 Axis

2020 ◽  
Author(s):  
Wei Hong ◽  
Zhanying Wei ◽  
Zhaohui Qiu ◽  
Zheng Li ◽  
Chensheng Fu ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Western Blot ◽  
Bone Microarchitecture ◽  
In Vitro Study ◽  
Control Group ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Resorption Marker ◽  
Related Transcription Factor

Abstract Background Statins are the most widely used drugs in elderly patients, the most common clinical application of statins is in aged hyperlipemia patients. There are few studies on the effects and mechanisms of statins on bone in elderly mice with hyperlipemia. The study is to examine the effects of atorvastatin on bone phenotypes and metabolism in aged apolipoprotein E-deficient (apoE–/–) mice, and the possible mechanisms involved in these changes. Methods Twenty-four 60-week-old apoE–/– mice were randomly allocated to two groups. Twelve mice were orally gavaged with atorvastatin (10 mg/kg body weight/day) for 12 weeks; the others served as the control group. Bone mass and skeletal microarchitecture were determined using micro-CT. Bone metabolism was assessed by serum analyses, qRT-PCR, and Western blot. Bone marrow-derived mesenchymal stem cells (BMSCs) from apoE–/– mice were differentiated into osteoblasts and treated with atorvastatin and Sirt1 inhibitor EX-527. Results The results showed that long-term administration of atorvastatin increases bone mass and improves bone microarchitecture in trabecular bone but not in cortical bone. Furthermore, the serum bone formation marker osteocalcin (OCN) was ameliorated by atorvastatin, whereas the bone resorption marker tartrate-resistant acid phosphatase 5b (Trap5b) did not appear to be impacted by atorvastatin treatment. The mRNA expression of Sirt1, runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and OCN in bone tissue were increased after atorvastatin administration. Western blot showed same trend in Sirt1 and Runx2. The in vitro study showed that when BMSCs from apoE–/– mice were pretreated with EX527, the higher expression of Runx2, ALP and OCN activated by atorvastatin decreased significantly or showed no difference compared with the control. The protein expression of Runx2 showed same trend. Conclusions Accordingly, the current study validates the hypothesis that atorvastatin can increase bone mass and promote osteogenesis in aged apoE−/− mice by regulating the Sirt1–Runx2 axis.

scholarly journals Beraprost ameliorates postmenopausal osteoporosis by regulating Nedd4-induced Runx2 ubiquitination

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Huo-Liang Zheng ◽  
Wen-Ning Xu ◽  
Wen-Sheng Zhou ◽  
Run-Ze Yang ◽  
Peng-Bo Chen ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Postmenopausal Osteoporosis ◽  
Vital Role ◽  
Therapeutic Drug ◽  
Dependent Manner ◽  
Bone Mesenchymal Stem Cells ◽  
Related Transcription Factor ◽  
Neuronal Precursor Cell

AbstractBone health requires adequate bone mass, which is maintained by a critical balance between bone resorption and formation. In our study, we identified beraprost as a pivotal regulator of bone formation and resorption. The administration of beraprost promoted differentiation of mouse bone mesenchymal stem cells (M-BMSCs) through the PI3K–AKT pathway. In co-culture, osteoblasts stimulated with beraprost inhibited osteoclastogenesis in a rankl-dependent manner. Bone mass of p53 knockout mice remained stable, regardless of the administration of beraprost, indicating that p53 plays a vital role in the bone mass regulation by beraprost. Mechanistic in vitro studies showed that p53 binds to the promoter region of neuronal precursor cell-expressed developmentally downregulated 4 (Nedd4) to promote its transcription. As a ubiquitinating enzyme, Nedd4 binds to runt-related transcription factor 2 (Runx2), which results in its ubiquitination and subsequent degradation. These data indicate that the p53–Nedd4–Runx2 axis is an effective regulator of bone formation and highlight the potential of beraprost as a therapeutic drug for postmenopausal osteoporosis.

In-vitro analysis of rhBMP-2 effects in human osteogenic cells

2013 ◽  
Vol 91 (11) ◽  
pp. 929-934
Author(s):  
Eder M.F. de Oliveira ◽  
Elizabeth F. Martinez ◽  
Jeruza P. Bossonaro ◽  
Renato C. Ribeiro ◽  
Vera C. de Araújo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
In Vitro Study ◽  
Bone Morphogenetic Protein 2 ◽  
Control Group ◽  
Osteoblastic Cell ◽  
Noncollagenous Proteins ◽  
Western Blot Assay ◽  
Osteoblastic Cell Line

This study evaluated the in vitro expression of bone-related proteins by osteoblasts in the presence of different concentrations of human recombinant bone morphogenetic protein-2 (rhBMP-2). Immortalized human fetal osteoblastic cell line 1.19 (hFOB) were exposed to different concentrations of rhBMP-2 (10, 50, or 100 ng/mL) for 72 h. Cell proliferation and viability (MTT assay), as well as the expression of fibronectin, osteonectin, and osteopontin were assessed by indirect immunofluorescence and Western blot. Neither of the 3 concentrations of rhBMP-2 caused statistically significant alterations in cell proliferation and viability, although the concentration of 100 ng/mL showed lower values for both assays after both 48 and 72 h of exposure. There was no alteration in the expression of noncollagenous proteins, as analyzed by immunofluorescence, when compared with the control group. Furthermore, in the Western blot assay we observed a statistically significant decrease in fibronectin and osteonectin at 100 ng rhBMP-2/mL (p < 0.05) by comparison with the medium alone. The expression of osteopontin decreased slightly in all 3 concentrations of rhBMP-2 tested; however, the change was not statistically significant (p > 0.05). In this in-vitro study, the tested concentrations of rhBMP-2 appeared to decrease the expression of important bone-related molecules in pre-osteoblast cells.

scholarly journals Plasma leptin concentrations in postmenopausal women with osteoporosis

2000 ◽  
pp. 170-173 ◽  
Author(s):  
E Odabasi ◽  
M Ozata ◽  
M Turan ◽  
N Bingol ◽  
A Yonem ◽  
...  
Keyword(s):  
Bone Mass ◽  
Postmenopausal Women ◽  
Patient Group ◽  
Bone Mineral ◽  
In Vitro Study ◽  
Control Group ◽  
Mineral Density ◽  
Median Plasma ◽  
Plasma Leptin

BACKGROUND: The obese are usually protected against osteoporosis and have increased bone mineral density and plasma leptin concentrations. A recent in vitro study demonstrated that leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts, suggesting an influence of leptin on bone mass. However, little is known about the relationship between plasma leptin and bone mass in postmenopausal women with osteoporosis. OBJECTIVE: To investigate plasma leptin concentrations in postmenopausal women with osteoporosis to improve the understanding of the role of leptin in determining bone mass. METHODS: Fifty postmenopausal women with osteoporosis (ages 61.18+/-6.51 years; body mass index (BMI) 28. 91+/-3.44kg/m(2), mean+/-s.d.) and 30 age- and BMI-matched healthy postmenopausal women were included in the study. Bone mineral densities (BMD) were measured by dual energy X-ray absorptiometry. Plasma leptin concentrations were determined using an immunoradiometric assay. RESULTS: The median spine BMD value in the patient group (0.695+/-8.26g/cm(2), median+/-s.e.m.) was significantly lower than that in the control group (1.006+/-1. 29g/cm(2), median+/-s.e.m.; z=-7.454, P<0.001). The median plasma leptin concentration in the patient group (18.70+/-1.78ng/ml, median+/-s.e.m.) was not significantly different from that in the control group (22.35+/-2.20ng/ml, median+/-s.e.m.; z=-1.630, P=0. 103). Plasma leptin concentrations were correlated with BMI in both groups (r(s)=0.394, P=0.031 in controls and r(s)=0.404, P=0.004 in the patient group). There was no correlation between plasma leptin concentrations and BMD values in controls (r(s)=-0.107, P=0.575) but a weak correlation was observed in the patient group (r(s)=0.285, P=0.045). CONCLUSION: Our data suggest that circulating plasma leptin does not have a significant direct influence on bone mass in postmenopausal women.

Reverse torque values of abutment screws after dynamic loading: The effects of sealant agents and the taper of conical connections

2020 ◽  
Author(s):  
Arda Ozdiler ◽  
suleyman dayan ◽  
Burc Gencel ◽  
Gulbahar Isık-Ozkol
Keyword(s):  
Dynamic Loading ◽  
Antibacterial Agent ◽  
In Vitro Study ◽  
Control Group ◽  
Silicone Sealant ◽  
Reverse Torque ◽  
The Stability ◽  
Torque Values ◽  
Chlorhexidine Gel

This in vitro study evaluated the influence of taper angles on the internal conical connections of implant systems and of the application of chlorhexidine gel as an antibacterial agent or a polyvinyl siloxane (PVS) sealant on the reverse torque values of abutment screws after dynamic loading. The current study tested four implant systems with different taper angles (5.4°, 12°, 45°, and 60°). Specimens were divided into three groups: control (neither chlorhexidine gel filled nor silicone sealed), 2% chlorhexidine gel-filled or silicone-sealed group, and group subjected to a dynamic load of 50 N at 1 Hz for 500,000 cycles prior to reverse torque measurements. Quantitative positive correlation was observed between the taper angle degree and the percentage of tightening torque loss. However, this correlation was significant only for the 60° connection groups except in the group in which a sealant was applied ( p = 0.013 for the control group, p = 0.007 for the chlorhexidine group). Percentages of decrease in the torque values of the specimens with silicone sealant application were significantly higher compared with both the control and chlorhexidine groups ( p = 0.001, p = 0.002, p = 0.001, and p = 0.002, respectively, according to the increasing taper angles); the percentage of decrease in torque values due to chlorhexidine application was statistically insignificant when compared with the control group. The application of gel-form chlorhexidine as an antibacterial agent does not significantly affect the stability of the implant–abutment connection under dynamic loads. PVS sealants may cause screw loosening under functional loads.

Comparative Study to Evaluate the Surface Detail Reproduction of Dental Stone after Immersion in Various Different Disinfectant Solutions, Under Stereomicroscope 10 X Magnification –An In-Vitro Study

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Rathika Rai ◽  
M. A. Easwaran ◽  
K. T. Dhivya
Keyword(s):  
Sodium Hypochlorite ◽  
In Vitro Study ◽  
Control Group ◽  
Immersion Method ◽  
Significant Difference ◽  
Surface Irregularities ◽  
Disinfectant Solution ◽  
Surface Detail ◽  
Group B

Aim: To evaluate the surface detail reproduction of dental stone this is immersed in different disinfectant solution and studied under stereomicroscope. Methodology: Total number of 30 specimens of dental stone (Type III) were made with measurements of 1.5cm diameter and 1cm height .This samples are divided in to 3 groups group A,B,C. were A is immersed in Distilled water which was taken as control group ;B is immersed in 2% Glutaraldehyde and C is immersed in 5%sodium hypochlorite. Each specimen were immersed in the disinfectant solution for 15 minutes and dried under room temperature for 24 hrs. After 24 hrs each specimens are studied under stereomicroscope for surface details. Result: The results showed no significant difference in the surface irregularities and porosities for a group 1 and group 2 except group 3 which showed significant increase in the porosities, surface irregularities and erosions after disinfection with 5% NaHOCl by immersion method. Conclusion: The surface detail reproduction capacity of die stone was adversely affected when 5% Sodium hypochlorite was used as disinfectant solution when compare d to control group and 2% Glutaraldehyde

The changes in bone turnover markers of female systemic lupus erythematousus patients without glucocorticoid

Lupus ◽  
2021 ◽  
Vol 30 (6) ◽  
pp. 965-971
Author(s):  
Wang Tianle ◽  
Zhang Yingying ◽  
Hong Baojian ◽  
Gu Juanfang ◽  
Wang Hongzhi ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Metabolism ◽  
Bone Turnover Markers ◽  
Control Group ◽  
Bone Resorption Marker ◽  
Amino Terminal ◽  
Normal People ◽  
Turnover Markers

Objectives SLE is a chronic autoimmune disease, which can affect the level of bone metabolism and increase the risk of osteoporosis and fracture. The purpose of this research is to study the effect of SLE on bone turnover markers without the influence of glucocorticoids. Methods A total of 865 female subjects were recruited from Zhejiang Provincial People’s Hospital and the First Hospital of Jiaxing, including 391 SLE patients without the influence of glucocorticoids and 474 non-SLE people. We detected Bone turnover markers including amino-terminal propeptide of type 1 procollagen (P1NP), C-terminal turnover of β - I collagen (β-CTX), N-terminal midfragment of osteocalcin (NMID) and 25(OH)D, and analyzed the difference in Bone turnover markers between the SLE group and the control group, as well as the influence of age and season on bone metabolism in female SLE patients. Results In the SLE group, the average age was 43.93±13.95 years old. In the control group, the average age was 44.84±11.42 years old. There was no difference between the two groups (t = 1.03, P = 0.30). P1NP, NMID and 25(OH)D in the SLE group were significantly lower than those in the control group (Z = 8.44, p < 0.001; Z = 14.41, p < 0.001; Z = 2.19, p = 0.029), and β-CTX in the SLE group was significantly higher than that in the control group (Z = 2.61, p = 0.009). In addition, the levers of β-CTX, NMID, P1NP and 25(OH)D in older SLE female patients were statistically significantly higher than those in younger (ρ = 0.104, p = 0.041; ρ = 0.223, p < 0.001; ρ = 0.105, p = 0.038; ρ = 0.289, p < 0.001). Moreover, β-CTX reached a high value in summer and PINP reached a low value in winter. Conclusion The bone formation markers of female SLE patients without glucocorticoid were lower than those of normal people and the bone resorption marker was higher than that of normal people. The 25 (OH) D of female SLE patients without glucocorticoid was lower than that of normal people. The risk of osteoporosis and fracture may be higher in elderly women with SLE. The bone resorption level of female SLE patients is high in summer and the bone formation level is low in winter.

scholarly journals Pomegranate Peel Extract Is a Potential Alternative Therapeutic for Giardiasis

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 705
Author(s):  
Asmaa M. El-Kady ◽  
Iman A. M. Abdel-Rahman ◽  
Samer S. Fouad ◽  
Khaled S. Allemailem ◽  
Taghrid Istivan ◽  
...  
Keyword(s):  
Diarrheal Disease ◽  
Apoptotic Cell ◽  
In Vitro Study ◽  
Ethanolic Extract ◽  
Control Group ◽  
Pomegranate Peel ◽  
Pomegranate Peel Extract ◽  
Multiple Drugs ◽  
Peel Extract

Giardiasis is a major diarrheal disease affecting approximately 2.5 million children annually in developing countries. Several studies have reported the resistance of Giardia lamblia (G. lamblia) to multiple drugs. Therefore, identifying an effective drug for giardiasis is a necessity. This study examined the antiparasitic effect of Punica granatum (pomegranate) and evaluated its therapeutic efficacy in rats infected with G. lamblia. In vitro study showed high efficacy of pomegranate peel ethanolic extract in killing G. lamblia cysts as demonstrated by eosin vital staining. We showed that treating infected rats with pomegranate extract resulted in a marked reduction in the mean number of G. lamblia cysts and trophozoites in feces and intestine respectively. Interestingly, the number of G. lamblia trophozoites and cysts were significantly lower in the pomegranate extract-treated group compared to the metronidazole-positive control group. Moreover, pomegranate extract treatment significantly induced nitric oxide (NO) and reduced serum IL-6 and TNF-α, compared to infected untreated rats. Histological and scanning electron microscopy (SEM) examination of the jejunum and duodenum of pomegranate extract-treated animals confirmed the antiparasitic effect of the extract, and demonstrated the restoration of villi structure with reduction of villi atrophy, decreased infiltration of lymphocytes, and protection of intestinal cells from apoptotic cell death. In conclusion, our data show that the pomegranate peel extract is effective in controlling G. lamblia infections, which suggests that it could be a viable treatment option for giardiasis.

scholarly journals Potential of different fluoride gels to prevent erosive tooth wear caused by gastroesophageal reflux

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Philipp Körner ◽  
Luca Georgis ◽  
Daniel B. Wiedemeier ◽  
Thomas Attin ◽  
Florian J. Wegehaupt
Keyword(s):  
Gastroesophageal Reflux ◽  
Artificial Saliva ◽  
In Vitro Study ◽  
Tooth Wear ◽  
Control Group ◽  
Erosive Tooth Wear ◽  
Custom Made ◽  
Post Hoc ◽  
Bovine Enamel

Abstract Background This in-vitro-study aimed to evaluate the potential of different fluoride gels to prevent gastroesophageal reflux induced erosive tooth wear. Methods Surface baseline profiles of a total of 50 bovine enamel specimens [randomly assigned to five groups (G1–5)] were recorded. All specimens were positioned in a custom made artificial oral cavity and perfused with artificial saliva (0.5 ml/min). Reflux was simulated 11 times a day during 12 h by adding HCl (pH 3.0) for 30 s (flow rate 2 ml/min). During the remaining 12 h (overnight), specimens were stored in artificial saliva and brushed twice a day (morning and evening) with a toothbrush and toothpaste slurry (15 brushing strokes). While specimens in the control group (G1) did not receive any further treatment, specimens in G2–5 were coated with different fluoride gels [Elmex Gelée (G2); Paro Amin Fluor Gelée (G3); Paro Fluor Gelée Natriumfluorid (G4); Sensodyne ProSchmelz Fluorid Gelée (G5)] in the evening for 30 s. After 20 days, surface profiles were recorded again and enamel loss was determined by comparing them with the baseline profiles. The results were statistically analysed using one-way analysis of variance (ANOVA) followed by Tukey`s HSD post-hoc test. Results The overall highest mean wear of enamel (9.88 ± 1.73 µm) was observed in the control group (G1), where no fluoride gel was applied. It was significantly higher (p < 0.001) compared to all other groups. G2 (5.03 ± 1.43 µm), G3 (5.47 ± 0.63 µm, p = 0.918) and G4 (5.14 ± 0.82 µm, p > 0.999) showed the overall best protection from hydrochloric acid induced erosion. Enamel wear in G5 (6.64 ± 0.86 µm) was significantly higher compared to G2 (p = 0.028) and G4 (p = 0.047). Conclusions After 20 days of daily application, all investigated fluoride gels are able to significantly reduce gastroesophageal reflux induced loss of enamel.

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