The role of sirtuin 1 and its activator, resveratrol in osteoarthritis

Abstract

Osteoarthitis (OA) is the most common aging-related joint pathology; the aging process results in changes to joint tissues that ultimately contribute to the development of OA. Articular chondrocytes exhibit an aging-related decline in their proliferative and synthetic capacity. Sirtuin 1 (SIRT 1), a longevity gene related to many diseases associated with aging, is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase and master metabolic regulator. Along with its natural activator resveratrol, SIRT 1 actively participates in the OA pathological progress. SIRT 1 expression in osteoarthritic cartilage decreases in the disease progression of OA; it appears to play a predominantly regulatory role in OA. SIRT 1 can regulate the expression of extracellular matrix (ECM)-related proteins; promote mesenchymal stem cell differentiation; play anti-catabolic, anti-inflammatory, anti-oxidative stress, and anti-apoptosis roles; participate in the autophagic process; and regulate bone homeostasis in OA. Resveratrol can activate SIRT 1 in order to inhibit OA disease progression. In the future, activating SIRT 1 via resveratrol with improved bioavailability may be an appropriate therapeutic approach for OA.

Infrapatellar Fat Pad Stem Cells Responsiveness to Microenvironment in Osteoarthritis: From Morphology to Function

“…As previously described by López-Ruiz et al (2013), TEM analysis on OA-IFP stem cells evidenced a cytoplasm rich in transport/storage vesicles and deeply stained/electron dense structures, rough endoplasmic reticulum and mitochondria. Higher magnifications also suggested the presence of autolysosomes, a product of fusion of lysosomes (dark, electron dense vesicles) and autophagosomes (large, white vacuoles) that are deputed to autophagy (Revuelta and Matheu, 2017;Boya et al, 2018), a process that have been suggested to have a role in OA development (Deng et al, 2019). In fact, there is consensus in claiming that autophagy can be triggered by a variety of internal or external stimuli as well as hypoxia, Reactive Oxygen Species (ROS) and accumulation of unfolded proteins, which are all conditions typically encountered in OA (Hughes et al, 2017).…”

Effect of Resveratrol on In Vitro and In Vivo Models of Diabetic Retinophathy: A Systematic Review

“…SIRTs are linked with several signaling pathways regulating inflammation attenuation, DNA damage repair, apoptosis, redox status and others [43]. Resveratrol was proposed to exert its anti-inflammatory and antioxidative actions as well as suppression of tumorigenesis and vasodilation through activation of SIRT1 [9,44].…”

Paeonol Ameliorates Inflammation and Cartilage of Chondrocytes in Osteoarthritis by Upregulating SIRT1

“…SIRT has been elucidated to exert its anti-in ammatory effect and regulate ECM in OA [20], and overexpression of SIRT1 in human chondrocytes leads to repression of MMP-3, MMP-8 and MMP-13 expressions [21]. Herein, we found that SIRT1 expression was hampered in the chondrocytes treated with IL-1β, while paeonol treatment could dose-dependently increase SIRT expression.…”