Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

Wang, Xiaowei; Chen, Liaobin; Peng, Wei

doi:10.3892/etm.2017.5147

Cited by 34 publications

(54 citation statements)

References 34 publications

(41 reference statements)

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“…The OVX rats presented bone loss and weight gain. In addition, the resveratrol treatment alleviated osteoporosis symptoms, which were in agreement with other publications [32,33].…”

Section: Discussionsupporting

confidence: 92%

Resveratrol promotes osteoblastic differentiation in a rat model of postmenopausal osteoporosis by regulating autophagy

et al. 2020

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Objective: Resveratrol is a natural polyphenolic compound that ameliorates postmenopausal osteoporosis by activating the estrogen receptor. Research has shown that resveratrol exhibits some type of estrogen receptor agonist activity, reducing the risk of breast cancer. However, its mechanism of action remains largely unknown. This study aims to investigate the effect of resveratrol on osteoblastic and osteoclastic differentiation and its potential role in the regulation of autophagy. Methods: Sprague Dawley (SD) rats underwent ovariectomies (OVX) and were administered resveratrol (at 10, 20 or 40 mg/kg/d) for 8 weeks. The calcium content and the bone mineral density (BMD) were measured in the lumbar vertebrae (L3) and the right distal femur-tibia bone region. The osteoblasts and osteoclasts were isolated from rat lumbar vertebrae by enzyme digestion and bone marrow induction, respectively. The cells were then cultured with resveratrol in combination with bafilomycin or leupeptin to inhibit or activate autophagy, respectively. Western blotting was used to assess the differentiation markers and autophagy-related genes in the osteoblasts and osteoclasts. Results: Compared to the sham group, the bone calcium content and BMD were significantly decreased in the OVX group (p < 0.05), while resveratrol attenuated these in a dose-dependent manner. In the osteoblasts, vascular endothelial growth factor (VEGF), and alpha-1 type I collagen (COL1A1) were markedly decreased, and in osteoclasts, the receptor activator of nuclear factor-κB ligand (RANKL) was increased in the OVX group, while resveratrol reversed this pattern in a dose-dependent manner. The inhibition of autophagy in osteoblasts and its activation in osteoclasts was observed in the OVX group. However, with resveratrol, this was reversed in a dosedependent manner. Conclusion: Overall, resveratrol promotes osteoblastic differentiation and suppresses osteoclastic differentiation in a rat model with postmenopausal osteoporosis by regulating autophagy.

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“…The OVX rats presented bone loss and weight gain. In addition, the resveratrol treatment alleviated osteoporosis symptoms, which were in agreement with other publications [32,33].…”

Section: Discussionsupporting

confidence: 92%

Resveratrol promotes osteoblastic differentiation in a rat model of postmenopausal osteoporosis by regulating autophagy

et al. 2020

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“…Consistent with our findings that NO‐releasing compounds stimulate osteoblast differentiation and bone formation, NO‐donors also antagonize ovariectomy‐ or corticosteroid‐induced bone loss in rodents (Wimalawansa et al ., ; Hukkanen et al ., ) and improve fracture healing (Corbett et al ., ; Diwan et al ., ). Similarly, recent work suggests RSV might also be protective in an experimental model of osteoporosis in rats (Wang et al ., ), supporting our hypothesis that RSV might increase overall bone mass under normal conditions. However, whether such findings are truly translatable to human physiology remain to be determined where for example bioavailability of RSV and lifestyle factors may enhance or diminish the effects observed in rodent models (Tome‐Carneiro et al ., ; Berman et al ., ).…”

Section: Discussionsupporting

confidence: 89%

“…RSV promotes osteoblast differentiation from mesenchymal stem cells in vitro (Zhou et al ., ; Kupisiewicz et al ., ; Shakibaei et al ., ), reduces the formation of bone‐resorbing osteoclasts (Shakibaei et al ., ) and may be protective in an experimental model of accelerated bone disease (Wang et al ., ) suggesting that RSV supplementation may be beneficial for bone health to prevent the age‐related decline in functional integrity or as an experimental medicine in disorders of excessive bone destruction. However, the intracellular mechanisms activated by RSV stimulation remain complex and convoluted.…”

Section: Introductionmentioning

confidence: 99%

The polyphenol resveratrol promotes skeletal growth in mice through a sirtuin 1‐bone morphogenic protein 2 longevity axis

Zhao

Garrett

et al. 2018

British J Pharmacology

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Background and PurposeThe polyphenol resveratrol (RSV) exists in high quantities in certain foods (e.g. grapes and nuts). However, the capacity of RSV to confer physiological health benefits and a biological mechanism through which this might occur remains unclear.Experimental ApproachAged, RSV‐treated (300 mg·kg−1·day−1) and genetically modified [endothelial NOS (eNOS−/−)] female mice were assessed using histomorphometric and μCT analysis. Alongside in vivo analysis, molecular siRNA knockdown and pharmacological manipulation of eNOS, BMP2 and sirtuin 1 (SIRT1) and functional cellular assays in an osteoblast cell line panel, explored the mechanism through which RSV might impact overall bone volume.Key ResultsRSV promoted osteoblast activity and bone growth in vivo. RSV dose‐dependently and simultaneously increased alkaline phosphatase (ALP) and eNOS levels. Similarly, NO‐donor treatment increased ALP, runt homology transcription factor 2, BMP2 and stimulated bone formation, whilst eNOS‐deficient mice displayed a bone loss phenotype. Moreover, RSV‐induced increase in ALP and BMP2 expression was blocked in eNOS−/− osteoblasts and by BMP‐inhibitor noggin. The longevity‐linked SIRT1 enzyme was positively regulated by RSV and SIRT1 deletion reduced eNOS, BMP2 and ALP. Like eNOS deletion, loss of SIRT1 blocked RSV‐induced osteoblast activity; however, SIRT1 levels remained unchanged in eNOS−/− mice, indicating RSV activation of SIRT1 stimulates BMP2 release via eNOS. This signalling axis is supported by decreased SIRT1, eNOS and BMP2 confirmed in old versus young bone.Conclusions and ImplicationsThese findings suggest a new mechanism of action in bone remodelling and the ageing skeleton, where RSV positively impacts bone homeostasis via SIRT1 activation of BMP2.

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“…Previous studies have indicated the beneficial effects of sirtuins as the best small molecule that activate sirtuins, which extended lifespan in a yeast model [104][105][106][107][108][109]. Although only the longevity extension effect of resveratrol has been reported in C. elegans and D. melanogaster, many subsequent studies reported that resveratrol intake promotes health and plays a preventive role in age-related diseases, such as cancer [110][111][112][113], atherosclerosis [114,115], arthritis [116,117], cataract [118][119][120], cardiovascular disease [121], hypertension [122,123], type 2 diabetes [124][125][126][127], osteoporosis [128][129][130], and Alzheimer disease [131][132][133]. In clinical studies, resveratrol intake improved the memory capacity of elderly individuals and reduced blood lipid levels in obese and type 2 diabetic patients [134,135].…”

Section: Resveratrolmentioning

confidence: 99%

Anti-Aging Effects of Calorie Restriction (CR) and CR Mimetics Based on the Senoinflammation Concept

et al. 2020

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Chronic inflammation, a pervasive feature of the aging process, is defined by a continuous, multifarious, low-grade inflammatory response. It is a sustained and systemic phenomenon that aggravates aging and can lead to age-related chronic diseases. In recent years, our understanding of age-related chronic inflammation has advanced through a large number of investigations on aging and calorie restriction (CR). A broader view of age-related inflammation is the concept of senoinflammation, which has an outlook beyond the traditional view, as proposed in our previous work. In this review, we discuss the effects of CR on multiple phases of proinflammatory networks and inflammatory signaling pathways to elucidate the basic mechanism underlying aging. Based on studies on senoinflammation and CR, we recognized that senescence-associated secretory phenotype (SASP), which mainly comprises cytokines and chemokines, was significantly increased during aging, whereas it was suppressed during CR. Further, we recognized that cellular metabolic pathways were also dysregulated in aging; however, CR mimetics reversed these effects. These results further support and enhance our understanding of the novel concept of senoinflammation, which is related to the metabolic changes that occur in the aging process. Furthermore, a thorough elucidation of the effect of CR on senoinflammation will reveal key insights and allow possible interventions in aging mechanisms, thus contributing to the development of new therapies focused on improving health and longevity.

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Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

Cited by 34 publications

References 34 publications

Resveratrol promotes osteoblastic differentiation in a rat model of postmenopausal osteoporosis by regulating autophagy

Resveratrol promotes osteoblastic differentiation in a rat model of postmenopausal osteoporosis by regulating autophagy

The polyphenol resveratrol promotes skeletal growth in mice through a sirtuin 1‐bone morphogenic protein 2 longevity axis

Anti-Aging Effects of Calorie Restriction (CR) and CR Mimetics Based on the Senoinflammation Concept

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