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

Zhenhan Deng,Shengshi Xiao,Jian Tian,Yusheng Li,Liangjun Li,Chao Cheng,Greg Zhang,Haifeng Liu,Fangjie Zhang

doi:10.1042/bsr20190189

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.

Highlights

Osteoarthitis (OA), the most common aging-related joint pathology, is characterized by articular cartilage destruction along with changes occurring in other joint components, including bone, menisci, synovium, ligaments, capsule, and muscles [1]
The etiology of OA is mostly unclear, but several factors are suggested to be involved in the pathogenesis of OA, including mechanical, genetic, and aging-associated factors that lead to synovitis, apoptosis, and cartilage destruction
It has been recently confirmed that the Silent information regulator 2 type 1 is linked to various age-associated diseases such as obesity, type 2 diabetes, cardiovascular disease, cancer, dementia, arthritis, osteoporosis, as well as with OA [6]

Summary

Introduction

Osteoarthitis (OA), the most common aging-related joint pathology, is characterized by articular cartilage destruction along with changes occurring in other joint components, including bone, menisci, synovium, ligaments, capsule, and muscles [1]. Fisetin inhibits IL-1β-induced expression of nitric oxide (NO), PGE2, TNF-α, IL-6, COX-2, inducible nitric oxide synthase (iNOS), MMP 3, MMP 13, ADAMTS 5, and remarkably suppressed the degradation of SOX9, aggrecan, and collagen-II; it exerts all these anti-inflammatory effects through activating SIRT 1 [61].

Results

Conclusion