Resveratrol Modulates Bone Metabolism Through SIRT1-Mediated NF-κB Inhibition: Molecular Mechanisms and Therapeutic Implications.
5 affiliations
- 1Musculoskeletal Injuries Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- 2Department of Orthopedics, Imam Hossein Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- 3Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- 4Center for Genomics and Personalized Health, Queensland University, Brisbane, Australia.
- 5School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia.
Abstract
Osteoporosis and associated skeletal pathologies impose a staggering global health burden, disproportionately impacting elderly populations and postmenopausal women. At the root of excessive bone resorption and stalled osteogenesis lie persistent oxidative stress and chronic inflammation. Enter resveratrol, a naturally occurring polyphenol derived from red wine and grapes, which has surfaced as a compelling therapeutic candidate for skeletal preservation owing to its robust antioxidant and anti-inflammatory capacities. Herein, we evaluate the molecular pathways through which resveratrol governs bone metabolism, focusing sharply on SIRT1-driven suppression of NF-κB signaling. Integrating findings across cell cultures, animal models, and clinical trials yields a unified perspective on these osteoprotective mechanisms. Dual benefits define resveratrol's impact on skeletal architecture: it stimulates osteoblast differentiation and mineralization while suppressing osteoclastogenesis and bone resorption. Primarily, these outcomes stem from the activation of SIRT1, a NAD + -dependent deacetylase acting as a negative regulator of NF-κB transcription. Through SIRT1-mediated deacetylation of the NF-κB p65 subunit, the transcription of pro-inflammatory cytokines including IL-1β, TNF-α, and IL-6 diminishes, subsequently dampening RANKL-driven osteoclastogenesis. Simultaneously, through the SIRT1-dependent engagement of Nrf2/ARE pathways, antioxidant defenses are bolstered, sparing bone cells from oxidative stress-induced apoptosis. Substantial preclinical promise notwithstanding, hurdles persist regarding both systemic bioavailability and the standardization of ideal dosing protocols for bone preservation. This review provides a mechanistic framework to evaluate resveratrol as a viable nutraceutical modality for the prevention and management of osteoporosis.
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BibTeX
@article{khatami2026resveratrol,
title = {{Resveratrol Modulates Bone Metabolism Through SIRT1-Mediated NF-κB Inhibition: Molecular Mechanisms and Therapeutic Implications.}},
author = {Seyyed Hossein Khatami and Faezeh Gouhari and Alireza Manafi-Rasi and Maryam Fallah and Sajad Ehtiati and Ahmad Reza Ahmadi Abdashti and Mohsen Ariannik and Shahin Talebi and Diba Rafienejad and Mina Fakhrzadegan and Parasta Heidari and Reza Zandi},
journal = {Cell biochemistry and function},
year = {2026},
month = nov,
doi = {10.1002/cbf.70334},
url = {https://europepmc.org/article/MED/42968626},
note = {CC BY},
}
RIS
TY - JOUR
TI - Resveratrol Modulates Bone Metabolism Through SIRT1-Mediated NF-κB Inhibition: Molecular Mechanisms and Therapeutic Implications.
AU - Seyyed Hossein Khatami
AU - Faezeh Gouhari
AU - Alireza Manafi-Rasi
AU - Maryam Fallah
AU - Sajad Ehtiati
AU - Ahmad Reza Ahmadi Abdashti
AU - Mohsen Ariannik
AU - Shahin Talebi
AU - Diba Rafienejad
AU - Mina Fakhrzadegan
AU - Parasta Heidari
AU - Reza Zandi
PY - 2026
DA - 2026/11/01
JO - Cell biochemistry and function
DO - 10.1002/cbf.70334
UR - https://europepmc.org/article/MED/42968626
AB - Osteoporosis and associated skeletal pathologies impose a staggering global health burden, disproportionately impacting elderly populations and postmenopausal women. At the root of excessive bone resorption and stalled osteogenesis lie persistent oxidative stress and chronic inflammation. Enter resveratrol, a naturally occurring polyphenol derived from red wine and grapes, which has surfaced as a compelling therapeutic candidate for skeletal preservation owing to its robust antioxidant and anti-inflammatory capacities. Herein, we evaluate the molecular pathways through which resveratrol governs bone metabolism, focusing sharply on SIRT1-driven suppression of NF-κB signaling. Integrating findings across cell cultures, animal models, and clinical trials yields a unified perspective on these osteoprotective mechanisms. Dual benefits define resveratrol's impact on skeletal architecture: it stimulates osteoblast differentiation and mineralization while suppressing osteoclastogenesis and bone resorption. Primarily, these outcomes stem from the activation of SIRT1, a NAD + -dependent deacetylase acting as a negative regulator of NF-κB transcription. Through SIRT1-mediated deacetylation of the NF-κB p65 subunit, the transcription of pro-inflammatory cytokines including IL-1β, TNF-α, and IL-6 diminishes, subsequently dampening RANKL-driven osteoclastogenesis. Simultaneously, through the SIRT1-dependent engagement of Nrf2/ARE pathways, antioxidant defenses are bolstered, sparing bone cells from oxidative stress-induced apoptosis. Substantial preclinical promise notwithstanding, hurdles persist regarding both systemic bioavailability and the standardization of ideal dosing protocols for bone preservation. This review provides a mechanistic framework to evaluate resveratrol as a viable nutraceutical modality for the prevention and management of osteoporosis.
SN - 0263-6484
SN - 1099-0844
ER -