Tsai et al. EC Gynaecology. Sassarini J, Lumsden MA. JZ and GZ: Resveratrok equally to this work.

Resveratrol and bone health -

Sulfonylureas and risk of falls and fractures among nursing home residents with type 2 diabetes mellitus. Diab Res Clin. Download references. Department of Medical Sciences, University of Turin, Turin, Italy.

Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy. You can also search for this author in PubMed Google Scholar. participated in the conception and design of the study, supervision of data collection, data analysis, interpretation of the findings of the study, and manuscript writing and revision.

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A double-blind randomized-controlled trial. Download citation. Received : 02 March Revised : 26 July Accepted : 22 August Published : 20 September Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. BMC Complementary Medicine and Therapies Journal of Orthopaedic Surgery and Research Skip to main content Thank you for visiting nature. Download PDF. Subjects Diabetes complications Randomized controlled trials.

Abstract Objectives Patients with type 2 diabetes T2DM are at increased fracture risk. Results At follow-up, calcium concentrations increased in all patients, while within-group variations in alkaline phosphatase were higher in both resveratrol arms, and hydroxy vitamin D increased in the Resv arm only, without between-group differences.

Introduction Type 2 diabetes T2DM subjects are at a higher risk for bone fracture due to altered bone cell function and bone remodeling, advanced glycation end-product AGE accumulation causing collagen deterioration, and microarchitectural changes 1 , 2. Subjects and methods Participants Participants were enrolled at the Diabetic Clinic of the Department of Medical Sciences of the University of Turin, between October and February Study design The present study was a double-blind, randomized, placebo-controlled trial, and has been registered in December at clinicaltrials.

Compliance Compliance with the study protocol was monitored with monthly phone calls and pill counting. Blinding The bottles containing resveratrol and placebo capsules were identical and were prepared by a person who did not take part in the study and were labeled with patient identification number.

Ethical aspects All procedures were in agreement with the principles of the Helsinki Declaration; the study protocol was approved by the Local Ethics Committee. Measurements At baseline and after 6 months trial end , data related to health status, the use of drugs or supplements, and usual dietary habits and exercise levels were collected from all subjects.

DXA was used to determine lean and fat body mass, using whole-body absorptiometry software. Blood samples, collected after an overnight fast, were centrally analyzed. Statistical methods The sample size was originally calculated for another outcome, the reduction of C-reactive protein CRP : to obtain an effect size of 0.

Table 1 Baseline variables by arm of the trial Full size table. Table 2 Comparisons on change from baseline of the analyzed variables Full size table.

Full size image. Discussion Resveratrol supplementation was associated with positive effects on bone density in patients with T2DM, and particularly in those with unfavorable conditions at baseline. Subgroup analyses Resveratrol seemed to be more effective on BMD in subgroups with unfavorable baseline characteristics, i.

Limitations This trial has a few limitations, such as the unfeasibility of DXA for evaluation of changes in bone geometry and microstructure; the precision error of DXA measurements increases with higher BMI; biochemical markers of bone turnover and serum parathormone levels were not measured; the determination of circulating variables does not necessarily reflect actions at the tissue level; even if our study had the longest time duration among published human trials, it could not determine the impact of resveratrol on the fracture risk, the major bone complication of T2DM patients.

Conclusion In conclusion, the supplementation with resveratrol was associated with slight beneficial effects on bone density in patients with T2DM, especially in specific high-risk subgroups of patients. References Rubin, M. Article Google Scholar Carnevale, D. Article CAS Google Scholar Tomé-Carneiro, J.

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Additional information Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic supplementary material. Flow of the study. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.

About this article. Cite this article Bo, S. Copy to clipboard. This article is cited by Morphological and biomechanical characterization of long bones and peri-implant bone repair in type 2 diabetic rats treated with resveratrol Carolina Sayuri Wajima Letícia Pitol-Palin Roberta Okamoto Scientific Reports Effects of resveratrol supplementation on bone quality: a systematic review and meta-analysis of randomized controlled trials Qiangqiang Li Guangpu Yang Wayne Yuk-wai Lee BMC Complementary Medicine and Therapies Nutritional Supplements and Skeletal Health Laila S.

Tabatabai Deborah E. Sellmeyer Current Osteoporosis Reports Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells Dong Kyu Moon Bo Gyu Kim Dong Kyun Woo Journal of Orthopaedic Surgery and Research About the journal Journal Information Open Access Publishing About the Editors Contact For Advertisers.

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Metrics details. The results from clinical trials have revealed that the effects of resveratrol supplementation on bone mineral density BMD and bone biomarkers are inconsistent. Our objective was to determine the effects of resveratrol supplementation on BMD and serum bone biomarkers.

PubMed, Cochrane library, EMBASE, Web of science and Scopus were searched up to August 24, Two reviewers independently performed the articles search and screen according to defined selection criteria.

The study quality of the randomized controlled trials RCTs was evaluated with the Cochrane scoring system. Heterogeneity among studies was examined by Cochrane Q test.

Retrieved data were pooled after mean differences MD were computed between two groups for BMD and serum biomarkers. Subgroup analyses were performed to evaluate a potential difference in terms of dose of resveratrol and intervention duration.

Sensitivity analysis was executed by omitting studies with imputed values in order to evaluate the influence of these studies on the overall results.

Ten eligible studies involving subjects were included in this meta-analysis with participants receiving resveratrol and receiving placebo. Supplementation of resveratrol had no statistically significant effects on areal bone mineral density aBMD at lumbar spine MD: Supplementation of resveratrol also did not result in significant change in bone serum markers, including serum alkaline phosphatase ALP , bone alkaline phosphatase BAP , osteocalcin OCN , procollagen I N-terminal propeptide PINP , C-terminal telopeptide of type I collagen CTX and parathyroid hormone PTH.

Subgroup analysis showed the effect of resveratrol supplementation on BMD and serum bone markers were similar in trails of different doses, intervention duration, and pathological conditions of the participants. Resveratrol supplementation did not show any significant effect on BMD or serum bone markers with the current evidence.

Further investigation with more well-organized multicentre randomized trial is warranted. Peer Review reports. Osteoporosis is a skeletal disorder characterized by low bone mass, structural deterioration, decreased bone strength, and increased risk of fractures [ 1 ].

Osteoporosis has become one of the major challenging world-wide public health problems particularly in ageing societies [ 2 , 3 ]. Low bone mineral density BMD is a major risk factor for osteoporotic fracture, and it has been considered as a surrogate endpoint for fracture risk [ 4 ]. Current pharmacologic drugs that are used to treat osteoporosis mainly aim to reduce excessive bone resorption e.

estrogen and bisphosphonates or promote bone formation e. parathyroid hormone PTH , and to a lesser degree a combination of both e. anti-sclerostin antibody [ 5 ].

However, there is growing concern about the long-term use of these drugs due to their off-target effects [ 6 , 7 , 8 , 9 ]. Many preclinical studies have shown the protective effects of resveratrol exist in bone tissue in different animal models of osteoporosis [ 12 , 13 , 14 ].

The molecular mechanisms underlying the anti-osteoporotic effects of resveratrol were associated with its positive effect on osteogenesis and bone formation [ 15 , 16 ], inhibitory effect on osteoclastogenesis and bone resorption [ 17 , 18 ], antioxidative effect on bone cells [ 19 , 20 ], and promoting effect on the osteogenic differentiation of bone mesenchymal stem cells [ 21 , 22 ].

Therefore, resveratrol offers the promise of being an effective therapeutic target for osteoporosis through multiple actions on both osteoblasts and osteoclasts [ 1 ].

Despite the abovementioned preclinical evidence, randomized controlled trials of resveratrol supplementation on bone are explorative and show controversy [ 23 , 24 , 25 ], and therefore the effectiveness of resveratrol supplementation for improving bone quality is unclear.

A previous systematic review and meta-analysis compared bone biomarkers in subjects who received resveratrol or placebo. The results of the study showed a significant increase in serum alkaline phosphatase ALP and bone alkaline phosphatase BAP values after resveratrol treatment compared with placebo [ 26 ].

However, bone biomarkers only partially reflect the process of bone remodeling instead of bone quality outcome. Considering BMD is a surrogate endpoint for fracture risk that allows exploration of biological effects in clinical trials, and the effect of resveratrol supplementation on BMD has not been evaluated by meta-analysis till now.

Therefore, for the first time, we aimed to evaluate the effect of resveratrol supplementation on BMD and bone biomarkers through a systematic review and meta-analysis of available randomized clinical trials RCTs.

For this review, we followed the preferred reporting items for systematic reviews and meta-analyses PRISMA statement [ 27 ]. PubMed, Cochrane library, EMBASE, Web of science and Scopus were searched to retrieve relevant papers dating up to August 24, with no language restriction.

Our search strategy was based on a PICOS methodology and both Medical Subject Headings MeSh and text words were used supplementary Table 1. Literature search strategies were developed using terms which were related to resveratrol, bone density and bone biomarkers.

The reference lists of available studies were manually searched to identify additional articles for potential inclusions. The selection process was conducted by two individual investigators QQL and GPY independently and disagreements were resolved through discussions.

A flow diagram of our search strategy is depicted in Fig. Two reviewers QQL and GPY , working independently and in duplicate, identified and evaluated potentially eligible trials according to predefined inclusion criteria.

However, we excluded studies on non-human subjects, pregnant or lactating females. There were no restrictions on the administration method of resveratrol. However, we excluded studies in which extra intervention like hormone replacement therapy, bisphosphonates, and other drugs affecting bone metabolism were taken along with resveratrol.

We excluded studies in which the control group underwent additional therapies compared to intervention group, making it impossible to investigate the effects of resveratrol alone.

The secondary outcome measures were bone biomarkers ALP, BAP, PTH, osteocalcin OCN , C-terminal telopeptide of type I collagen CTX , N-terminal telopeptide of type I collagen NTX , and procollagen I N-terminal propeptide PINP.

Disagreements regarding the study selection process were resolved by discussion with the third researcher HTX. QQL extracted data from each eligible trial according to prepared data extraction form Table 1 and Table 2. The extracted data was checked by another investigator GPY to reduce reviewer errors.

If there were discrepancies, group consensus and a third reviewer was consulted to ensure accuracy of data. Data extracted from the eligible studies were: first author, year of publication, location of study, study population, characteristics of participants age, sex , number of participants in each group, loss to follow up, compliance, study duration and the final results of resveratrol supplementation comparisons with the control group, daily dose of resveratrol, route of administration, form of resveratrol, brand of resveratrol, purity of resveratrol, and any reported adverse events.

When the intermediary results of the clinical studies were reported at different time points of the study, only the final data at the end of the intervention period were considered for this review.

We used endpoint data rather than change data from baseline to maximise data availability considering most of the included studies 8 out of 10 studies did not report the change data from baseline and the standard deviation SD.

In addition, the comparison of final measurements in a randomized trial in theory estimates the same quantity as the comparison of changes from baseline [ 28 ]. For the single study in which BMD outcomes were presented as percentage change from baseline [ 23 ], and no endpoint data were available, we imputed endpoint data using the baseline BMD and percentage change from baseline and the SD of the baseline data for the endpoint SD [ 29 ].

Where studies reported absolute change from baseline and endpoint data were not available [ 30 ], we imputed endpoints using baseline plus change for the mean and using the SD of the baseline data for the endpoint SD.

If the data were only reported as graph, we extracted the values using GetData Graph Digitizer 2. If studies reported the median, range and the sample size, then the mean and SD were estimated [ 31 , 32 ]. For studies with more than one resveratrol dosage group, we divided the number in the control groups by the number of the treatment arms to avoid double-counting problem [ 28 ].

Two reviewers QQL and GPY , working independently and in duplicate, evaluated the quality of the eligible studies using the Cochrane scoring system [ 33 ] of 7 points based on the following criteria: 1 Random sequence generation, 2 Allocation concealment, 3 Blinding of participants and personnel, 4 Blinding of outcome assessment, 5 Incomplete outcome data, 6 Selective reporting, 7 Other sources of biases such as baseline imbalance.

Based on the recommendations of the Cochrane Handbook, risk of bias was judged to be L, H, and U, which is interpreted as low risk, high risk, and unknown risk of bias respectively. Subgroup analyses were performed by the dose of resveratrol and intervention period to determine whether the effects of supplementation varied by these factors.

Meta-analysis was conducted by combining studies which were clinically similar in participants, intervention, comparator and outcome PICO. All analyses were carried out using Review Manager 5. We used a random-effects model if a significant heterogeneity was detected; otherwise, a fixed-effects model was applied.

Studies containing different groups of resveratrol were independently entered. Funnel plots were not included in this study as tests for funnel plot asymmetry is not recommended when a meta-analysis contains fewer than 10 studies, due to the low power for detecting true effects not ascribed to chances [ 33 ].

We performed a sensitivity analysis by omitting studies for which data were imputed. Figure 1 shows the flow diagram of paper inclusion and selection process. In summary, a total of publications were identified from the following databases including PubMed 87 , Cochrane library 46 , EMBASE , Web of science , and Scopus , which yielded papers after removing duplicates articles.

Two additional relevant papers were recognized by searching the reference list of eligible publications. After screening the retrieved manuscripts based on titles and abstracts, we retrieved 20 full texts [ 23 , 24 , 25 , 35 ] [ 30 , 36 , 37 , 38 ] [ 39 , 40 , 41 ] [ 42 , 43 ] [ 44 , 45 ] [ 46 , 47 , 48 ] [ 49 ].

Table 1 describes the baseline characteristics of the included trials. Overall, 23 treatment arms were extracted from 10 RCTs that included a total of participants, of which participants were in the resveratrol group and were in the placebo group.

The year of publication of the included trials ranged from to Three trials were conducted in Denmark [ 23 , 35 , 36 ], two in Iran [ 37 , 38 ], one in the United State [ 30 ], one in Australia [ 25 ], one in Spain [ 39 ], and two in Italy [ 24 , 40 ]. Three studies were conducted on type 2 diabetes patients [ 24 , 37 , 39 ], two on patients with non-alcoholic fatty liver disease NAFLD [ 36 , 38 ], three on obese population [ 23 , 35 , 40 ], one on healthy elderly [ 30 ] and one on postmenopausal women [ 25 ].

Table 2 describes resveratrol intervention methods among the trials. All resveratrol supplements and placebos were in the form of capsules or tablets and were administrated orally either alone six in ten studies or in combination with other medications including antidiabetic, antiplatelets, antacids medications etc.

four in ten studies. Three of ten studies reported pre to post changes in BMD at lumbar spine, total hip and whole body [ 23 ] [ 24 ] [ 25 ], and all studies measured changes in serum bone biomarkers [ 23 , 24 , 25 , 30 , 35 , 36 ] [ 37 , 38 , 39 , 40 ], with three trials reporting serum OCN [ 23 , 25 ] [ 35 ], nine trials reporting ALP [ 23 , 24 , 35 , 36 ] [ 30 , 37 , 38 , 39 ] [ 40 ], two trials reporting PINP [ 23 ] [ 35 ], three trials reporting CTX [ 23 , 25 , 35 ], two trials reporting BAP [ 23 , 35 ] and two trials reporting PTH [ 23 , 35 ].

The risk of bias assessment was displayed in Fig. Three studies were considered to have unclear risk of bias for concealment and blinding procedures due to insufficient information of the procedures [ 23 , 30 , 35 ].

Three studies were rated high risk of bias for incomplete outcome data because they did not report the data of the final assessment [ 23 , 36 , 40 ].

One study was rated high risk of other sources of bias due to baseline imbalance [ 35 ]. Risk of bias assessment of the included studies. A total of three studies compared placebo with resveratrol on BMD [ 23 , 24 , 25 ].

As shown in Fig. The sensitivity analysis omitting studies that used imputed data also did not significantly affect the results supplementary Tables 2 , 3 and 4. Effects of resveratrol supplementation on bone mineral density. The funnel plots of main effects of resveratrol supplementation on BMD of a lumbar spine, b total hip, and c whole body.

Abbreviations: BMD, bone mineral density. There was no significant statistical heterogeneity between studies of the above outcomes. The sensitivity analysis suggested that the effect of resveratrol on serum ALP remains unchanged after omitting the studies with imputed values supplementary Table 5.

Effects of resveratrol supplementation on serum bone biomarkers. The funnel plots of main effects of resveratrol supplementation on a serum ALP, b serum BAP, c serum OCN, d serum PINP, e serum CTX, f serum PTH. Abbreviations: ALP, alkaline phosphatase; BAP, bone alkaline phosphatase; OCN, osteocalcin; PINP, procollagen I N-terminal propeptide; CTX, C-terminal telopeptide of type I collagen; PTH, parathyroid hormone.

Subgroup analysis also showed that the effects of resveratrol on serum ALP were not significantly changed by the pathological conditions of the participants, including participants with diabetes MD: 6.

Subgroup analysis of resveratrol supplements versus placebo on serum ALP. The funnel plots of subgroup analysis of the effects of a doses of resveratrol, b intervention duration, c doses and intervention duration, d with or without diabetes, d with or without NAFLD, and e with or without obesity on serum ALP.

Abbreviations: ALP, alkaline phosphatase; NAFLD, non-alcoholic fatty liver disease. Reporting of adverse events was limited, suggesting that resveratrol supplementation is well tolerated. Three RCTs reported the most frequent complaints were mild gastrointestinal symptoms including increased frequency of bowel motions and loose stools [ 23 , 30 , 36 ].

One study reported four adverse events, which were not necessarily attributable to the resveratrol supplementation [ 25 ]. The other studies reported that the rate of adverse events was low and the treatment was well tolerated [ 24 , 37 , 38 , 39 , 40 ]. The current meta-analysis aimed to evaluate the impact of resveratrol supplements on BMD and bone biomarkers compared with placebo.

Here, we revealed that resveratrol supplementation compared with placebo did not significantly increase BMD at lumbar spine, total hip and whole body.

In addition, resveratrol supplementation did not significantly change the expression of serum bone biomarkers including ALP, BAP, OCN, PINP, CTX and PTH. However, in view of the presence of some deficiencies among the included studies, such as the high risk of bias in some RCTs, the limited number of included studies and cases, and the clinical heterogeneity among the trials such as the dosage, intervention duration, and study population, the certainty of the current evidence is very low, which should be interpreted with caution.

Our findings are inconsistent with those of previous in vivo animal studies that suggested resveratrol supplementation increases BMD in aging, ovariectomy OVX and immobilization induced bone loss mouse models [ 12 , 13 , 14 ] and in vitro cellular studies that indicated resveratrol promotes osteoblast associated bone formation and inhibits osteoclast associated bone resorption [ 1 , 51 ].

Such discrepancies between animal and human clinical studies are not unexpectable. Firstly, results from in vitro studies should be interpreted with caution when trying to extrapolate the effect of resveratrol in vivo due to the influence of various complicated factors, including inter-species differences in terms of metabolism, absorption and tissue distribution, on the bioavailability of resveratrol in the target tissues [ 52 , 53 ].

Secondly, the dose-dependent effect of resveratrol on bone quality is not adequately studied in clinical studies. Recent evidence of more effective outcome at lower resveratrol doses may imply the need to have more adequate pharmacological studies in preclinical settings to justify the selection of more appropriate dose for clinical trials [ 54 , 55 ]..

Another problem is blood concentrations of resveratrol are often too low to be detected due to rapid absorption and clearance from the body [ 56 , 57 ], which limited the estimation of the effective doses of resveratrol in human. Development of novel delivery systems and resveratrol analogs with higher bioavailability [ 58 ] are of great interest in the future studies.

It is noteworthy that vitamin D could amplify the bioavailability of resveratrol [ 59 ], thus it would be interesting in the future to investigate if the combination of resveratrol and vitamin D could further improve its effect on bone density via addition effects on mineral homeostasis and bioavailability enhancement.

Thirdly, the intervention period of resveratrol is critical for the outcome of BMD. DXA scan is the most widely used procedure in the evaluation of BMD, however, BMD in human changes slowly with treatment thus the changes might not be detectable if the follow-up period is not adequately designed.

Therefore, caution should be taken when interpreting the results of any treatment on BMD outcome with short intervention period [ 60 ]. In this review, two RCTs evaluating the outcome of BMD had follow-up time shorter than one year, both of which reporting negative results of areal BMD aBMD between resveratrol and placebo group after resveratrol supplementation [ 23 , 24 ].

The study by Wong et al. with follow-up time more than one year reported that BMD significantly increased at lumbar spine by calculating the change from baseline between the placebo group and resveratrol group instead of the endpoint data [ 25 ].

It is noteworthy that in the study by Ornstrup et al. Future studies with longer follow-up time and QCT technique are needed to better elucidate the effects of resveratrol on BMD. A previous meta-analysis of randomized controlled trials on the effects of resveratrol on bone biomarkers concluded that resveratrol supplementation increased serum level of ALP and BAP without changes in other bone turnover markers such as PINP, CTX, OCN, and PTH [ 26 ].

Our review included four more RCTs and found no significant effect of resveratrol supplementation on serum ALP. Possible reasons for the discrepancy could be the four newly included studies showing opposite results, with two showing unchanged serum ALP after resveratrol supplementation [ 24 , 38 ], one showing significantly decreased ALP [ 39 ], and one showing significantly increased ALP level after resveratrol supplementation [ 40 ].

Another reason could be different types of data used in the meta-analysis. We used the endpoint data and the previous review used the change data from baseline. Nevertheless, it should be reminded that serum ALP is not a specific bone biomarker because it comes from several tissues including liver, kidney, intestine and bone [ 61 ].

apart from bone conditions [ 62 ]. On the other hand, BAP is the bone-specific isoenzyme of total ALP, which is considered as a more specific marker of osteoblastic activity. Our results showed a trend of increase in serum level of BAP following resveratrol supplementation, whereas the difference did not reach the statistical significance.

OCN is a small non-collagenous protein hormone synthetized by osteoblast during the mineralization of matrix and is used as a preliminary biomarker on the effectiveness of a drug on bone formation [ 63 ].

We did not see any significant difference following resveratrol supplementation, which is consistent with the previous review [ 26 ]. PINP is cleaved from type I procollagen by osteoblast, which reflects the integrated amount of skeletal new bone formation [ 64 ].

A Effects of different concentrations of resveratrol on MDM2 expression were measured by qRT-PCR. B p53 expression in different groups was assessed by qRT-PCR. C , D Osteogenic genes expression in different groups was measured by qRT-PCR and western blot.

E MDM2 expression in hMSCs after different treatments was assessed by qRT-PCR. F p53 expression in different groups was assessed by qRT-PCR. Although osteoporosis is a widespread disease [ 13 ] that has become a major challenge for public health systems worldwide [ 3 ], there is currently no gold standard treatment.

While resveratrol can reverse both osteoporosis-associated BMD reduction and microarchitectural deterioration [ 8 ], the mechanisms responsible for these effects remain unknown. In this study, 12 KEGG pathways associated with both osteoporosis and resveratrol-targeted genes were identified using bioinformatics tools.

Among these, the top five KEGG pathways with the smallest p values were prostate cancer pathway, pathway in cancer, glioma pathway, p53 pathway, and cell cycle pathway. Thus, resveratrol-targeted genes exerted biological effects primarily through the p53 signaling pathway.

p53 inhibits cancer development and progression via several mechanisms, including apoptosis, regulation of DNA replication, cell division, and inhibition of angiogenesis [ 14 , 15 ]. The p53 protein is encoded by the TP53 gene, which was identified in this study as the hub gene with the highest degree of interaction in the network.

TP53, CTNNB1, and SP1 modulate the expression of most of the differentially expressed genes that are upregulated and play important roles in primary osteoporosis [ 16 ]. Fu Jia et. In this study, both qRT-PCR and western blots indicated that p53 was enriched in osteoporosis Figure 6A , 6B.

In addition, qRT-PCR and Alizarin-red staining showed that MDM2-mediated inhibition of p53 induced osteoblast differentiation in vitro Figure 6C — 6G , indicating that p53 promoted the pathological progression of osteoporosis.

Accumulating evidence shows that resveratrol has anti-inflammatory, antioxidant, and other protective effects in osteoporosis and in aging-induced cognitive impairment [ 7 — 9 ]. Ali Mobasheri and Mehdi Shakibaei reported that resveratrol can modulate bone cell metabolism and bone turnover due to its osteogenic and osteoinductive properties [ 18 , 19 ].

In this study, resveratrol partially reversed pinduced inhibition of osteogenic differentiation in in vitro experiments Figure 7.

These results indicate that resveratrol may protect against osteoporosis by inhibiting the p53 signaling pathway. Some limitations in this study should be considered when interpreting the results. Firstly, the effects of different durations of resveratrol treatment were not investigated.

Furthermore, potential differences in p53 enrichment in different osteoporosis subtypes were not examined. Finally, additional studies are needed to compare the effects of resveratrol on osteoporosis development and progression with those of other drugs. In conclusion, bioinformatics analysis revealed that the protective effects of resveratrol against osteoporosis were associated with its interaction with the prostate cancer pathway, pathway in cancer, glioma pathway, p53 signaling pathway, and cell cycle signaling pathway.

Our in vitro experiment further indicated that resveratrol exerts anti-osteoporosis effects by inhibiting the p53 signaling pathway, and may thus serve as a promising osteoporosis treatment. The STITCH database integrates data on the effects of over chemicals on gene expression [ 20 ].

Resveratrol-targeted genes were identified using the default settings in STITCH, and the STITCH online tool was used to construct an interaction network for resveratrol and its targeted genes.

Degree, betweenness, and closeness were analyzed for each gene in the network and visualized using Cytoscape 3. Degree represents the extent to which one node is associated with all the other nodes in the network, closeness represents how far one node is from other nodes in the network, and betweenness is the number of times a node acts as the shortest bridge between two other nodes.

These measures for all resveratrol-targeted genes were then imported into Gephi software and a weighted interaction network was constructed. Enrichment information for the top five KEGG pathways was presented with GOplot, an R package that visually combines expression data with functional analysis [ 24 ].

Genes involved in all top five shared KEGG pathways were considered hub genes. Centrality in the network and chromosome position for all resveratrol-targeted genes were visualized using the circlize package for R [ 25 ].

The top five shared KEGG pathways with the smallest p values were selected, and KEGG pathways related to resveratrol-targeted genes were established, using Pathway Builder Tool 2.

Hub genes and their mechanisms of action are shown in the schematic diagrams. BMSCs were kindly donated by the Huazhong University of Science and Technology, Wuhan, China.

Cells were maintained for a maximum of 3 passages. Lipofectamine L, ThermoFisher Scientific, USA was used to transfect cells with siRNAs according to provided directions. MDM2 siRNA constructs RIBOBIO, Guangzhou, China were transfected at 50 nM.

Plasmid NC and plasmid MDM2 were synthesized by GenePharma company Shanghai, China. All in vitro experiments using cells were independently repeated three times. GAPDH was used as a housekeeping gene. Target gene expression was quantified using the ΔΔCT method.

The primers used in this study are listed in Table 2. Blots were then stained with appropriate horseradish peroxidase HRP -conjugated secondary antibodies AS, Aspen and proteins were detected with a chemiluminescence detection system. Each experiment was independently repeated three times.

BMSCs were grown in 6-well plates in media containing nM dexamethasone, 50 mM ascorbic acid, and 10 mM b-glycerophosphate to promote osteogenesis HUXMA, Cyagen, USA. Subsequently, 1 mL 0.

After rinsing with distilled water for 5 minutes, red mineralized nodules were analyzed via a charge-coupled device microscope. Absorbance was measured at nm.

Experiments were repeated in triplicate. Data are shown as means ± SD. GraphPad Prism 8. P Figure 8. YY and YX conceived of and designed the study; GY, HZ, and BL supervised the study; TY, ZW, and XY performed bioinformatics analysis and experiments; HZ and WH analyzed the data; JX and YZ provided advice and technical assistance; TY, ZW, and XY wrote the manuscript.

All authors approved the final manuscript.

The heapth standard double Healing ulcers naturally, randomised, Resveratrol and bone health research healh conducted eRsveratrol Denmark at Aarhus University Bonr gave Resveraatrol men with an hhealth age heealth 49 and body mass index BMI of The Amino acid structure endpoint was change Performance-boosting smoothies bone alkaline phosphatase BAP and this measure improved significantly over week study compared to placebo. Resveratrol is a powerful polyphenol and anti-fungal chemical that is often touted as the bioactive compound in grapes and red wine. Interest in the compound exploded in when research from David Sinclair and his team from Harvard reported that resveratrol was able to increase the lifespan of yeast cells. Other studies with only resveratrol have reported other benefits, including supporting heart health, blood sugar management, and energy endurance enhancement. Authors: Marie Juul Ornstrup, Torben Harsløf, Thomas Nordstrøm Kjær, Bente Lomholt Langdahl, Steen Bønløkke Pedersen. Cookies help us to provide Performance-boosting smoothies with Fatigue and diabetes management excellent service. By using our website, you declare Resveratrpl in agreement with our use bons cookies. Got It. Copyright © Rodman Media. All rights reserved. Use of this constitutes acceptance of our privacy policy The material on this site may not be reproduced, distributed, transmitted, or otherwise used, except with the prior written permission of Rodman Media. Login Join.

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