New Perspectives on Postmenopausal Osteoporosis: Mechanisms and Potential Therapeutic Strategies of Sirtuins and Oxidative Stress
Abstract
:1. Introduction
2. Core Mechanisms of Postmenopausal Osteoporosis
2.1. Effects of Estrogen on Bone Metabolism
2.2. Effects of Estrogen on OPG-RANKL-RANK and Wnt/β-Catenin Signaling Pathways
2.3. Effects of Estrogen on Immunity
3. Mechanisms of Sirtuins in Postmenopausal Osteoporosis
3.1. SIRT1
3.2. SIRT3
3.3. SIRT6
4. Sirtuins and Oxidative Stress
4.1. Mechanism of Oxidative Stress in Postmenopausal Osteoporosis
4.2. Interaction Between Sirtuins and Oxidative Stress
5. Targeted Activation of Sirtuins and Potential Therapeutic Strategies Against Oxidative Stress
5.1. Natural Activators of Sirtuins
5.2. Natural Antioxidants
6. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
PMOP | postmenopausal osteoporosis |
SIRTs | Sirtuins |
NAD+ | nicotinamide adenine dinucleotide |
OS | oxidative stress |
ROS | reactive oxygen species |
BMD | bone mineral density |
OB | osteoblast |
OC | osteoclast |
BMSCs | bone mesenchymal stem cells |
ERs | estrogen receptors |
Dkk1 | Inhibitor 1 |
SOST | Sclerostin |
Runx2 | Runt-related transcription factor 2 |
Osx | Osterix |
IL-1β | Interleukin-1β |
IL-6 | Interleukin-6 |
TNF-α | tumor necrosis factor-α |
IL-4 | interleukin 4 |
IL-10 | interleukin 10 |
NAD+ | Nicotinamide adenine dinucleotide |
ERα | Estrogen Receptor alpha |
FOXO | Forkhead box O |
PGC-1α | peroxisome proliferator-activated receptor γ coactivator 1-alpha |
NFATc1 | nuclear factor-activated T cell 1 |
TRAP | tartrate-resistant acid phosphatase |
CTSK | cathepsin K |
SOD2 | superoxide dismutase 2 |
FasL | Factor-related Apoptosis ligand |
GSH-Px | glutathione peroxidase |
NOX | reduced nicotinamide adenine dinucleotide phosphate oxidase |
XOD | xanthine oxidase |
4-HNE | 4-hydroxynonenal |
ILK | integrin-linked kinase |
GPX4 | glutathione peroxidase 4 |
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Sirtuins | Natural Activator | Sources | Biological Effects | Ref. |
---|---|---|---|---|
SIRT1 | Resveratrol | Grapes, red wine, blueberries, strawberries, peanuts, and mulberries | Reduce oxidative stress, regulate the SIRT1/PGC1α axis, and promote mitochondrial function | [92,93,94,95] |
Pterostilbene | Grapes, blueberries, cranberries, and peanuts | Regulate cell metabolism; reduce oxidative stress | [96,97,98] | |
Curcumin | Turmeric, curry, and mustard | Activate the Nrf2 signaling pathway and reduce oxidative stress | [99,100,101,102] | |
Quercetin | Onions, kale, blueberries, cranberries, and red wine | Regulate autophagy and reduce apoptosis of bone cells; reduce oxidative stress | [103,104,105] | |
Genistein | Soy, tofu, soy milk, and Pueraria | Mimic the role of estrogen and regulates bone metabolism; regulate cell metabolism | [106,107,108] | |
SIRT3 | Resveratrol | Grapes, red wine, blueberries, strawberries, peanuts, and mulberries | Activate Sirt3/FoxO3a pathway, up-regulate the expression of SOD2, and reduce the accumulation of ROS | [109,110] |
Curcumin | Turmeric, curry, and mustard | Inhibit the NF-κB signaling pathway; Rrgulate mitochondrial metabolism | [111,112] | |
Honokiol | Magnolia officinalis | Restrains NF-κB signaling pathway; promotes mitochondrial function | [113,114,115] | |
SIRT6 | Luteolin | Celery, green pepper, red pepper, broccoli, and spinach | Inhibit NF-κB signaling pathway; reduce oxidative stress | [116,117,118,119,120] |
Quercetin | Onions, kale, blueberries, cranberries, and red wine | Inhibit NF-κB signaling pathway; reduce oxidative stress | [116,118,119,120] | |
Anthocyanins | Blueberries, strawberries, mulberries, blackberries, grapes, and blackcurrants | Regulate glycolysis and energy metabolism; regulate mitochondrial metabolism | [121,122,123,124] | |
Catalpol | Rehmanniae Radix | Regulate cell metabolism; inhibit the NF-κB signaling pathway, alleviate inflammatory response, and reduce oxidative stress | [125,126,127] |
Natural Antioxidant | Sources | Biological Effects | Ref. | |
---|---|---|---|---|
Polyphenols | Resveratrol | Grapes, red wine, blueberries, strawberries, peanuts, and mulberries | Scavenge free radicals; inhibit NF-κB pathway; increase the up-regulation of the RUNX2 gene; reduce the activity of osteoclasts; reduce oxidative stress | [132,133] |
Curcumin | Turmeric, curry, and mustard | Inhibit NF-κB pathway; increase the up-regulation of the RUNX2 gene; reduce the activity of osteoclasts | [133] | |
Anthocyanins | Blueberries, strawberries, mulberries, blackberries, grapes, and blackcurrants | Regulate the RANKL pathway; inhibit oxidative stress; maintain the balance of bone metabolism | [134] | |
Pterostilbene | Grapes, blueberries, cranberries, and peanuts | Scavenge free radicals; activate the Nrf2 pathway; induce osteogenic activity | [135,136] | |
Fat-soluble antioxidant | Vitamin E | Wheat germ oil, sunflower oil, corn oil, peanut oil, almond, hazelnut, and cashew nut | Improve bone density and bone microstructure; scavenge ROS and free radicals | [137,138,139,140] |
Coenzyme Q10 | Pig heart, pig liver, chicken liver, beef, pork, and chicken | Activate the Nrf2 signaling pathway; regulate mitochondrial function | [141,142,143] | |
Lycopene | Tomatoes, watermelon, grapefruit, and carrots | Inhibit osteoclasts and promote osteoblasts | [144,145,146] | |
Water-soluble antioxidant | Vitamin C | Lemons, limes, grapefruit, oranges, strawberries, and raspberries | Scavenge free radicals and inhibit oxidative stress | [147,148] |
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Zhao, H.; Yu, F.; Wu, W. New Perspectives on Postmenopausal Osteoporosis: Mechanisms and Potential Therapeutic Strategies of Sirtuins and Oxidative Stress. Antioxidants 2025, 14, 605. https://doi.org/10.3390/antiox14050605
Zhao H, Yu F, Wu W. New Perspectives on Postmenopausal Osteoporosis: Mechanisms and Potential Therapeutic Strategies of Sirtuins and Oxidative Stress. Antioxidants. 2025; 14(5):605. https://doi.org/10.3390/antiox14050605
Chicago/Turabian StyleZhao, Huiying, Fan Yu, and Wei Wu. 2025. "New Perspectives on Postmenopausal Osteoporosis: Mechanisms and Potential Therapeutic Strategies of Sirtuins and Oxidative Stress" Antioxidants 14, no. 5: 605. https://doi.org/10.3390/antiox14050605
APA StyleZhao, H., Yu, F., & Wu, W. (2025). New Perspectives on Postmenopausal Osteoporosis: Mechanisms and Potential Therapeutic Strategies of Sirtuins and Oxidative Stress. Antioxidants, 14(5), 605. https://doi.org/10.3390/antiox14050605