Oleanolic Acid Decreases IL-1β-Induced Activation of Fibroblast-Like Synoviocytes via the SIRT3-NF-κB Axis in Osteoarthritis.

Jiapeng Bao,Lidong Wu,Ratanesh K Seth,Mengyao Chen,Weifeng Yan,Jisheng Ran,Kai Xu,Zhonggai Chen,Yan Xiong

doi:10.1155/2020/7517219

Jiapeng Bao, Lidong Wu + Show 7 more

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https://doi.org/10.1155/2020/7517219

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Abstract

Synovial inflammation is a major pathological feature of osteoarthritis (OA), which is a chronic degenerative joint disease. Fibroblast-like synoviocytes (FLS), localized in the synovial membrane, are specialized secretory cells. During OA synovitis, FLS produce chemokines and cytokines that stimulate chondrocytes to secrete inflammatory cytokines and activate matrix metalloproteinases (MMPs) in FLS. Recent studies have demonstrated that sirtuin 3 (SIRT3) performs as a key regulator in maintaining mitochondrial homeostasis in OA. This study aims at ascertaining whether SIRT3 is involved in OA synovitis. The overexpression (OE) and knockdown (KD) of SIRT3 are established by short hairpin RNA (shRNA) and recombinant plasmid in human FLS. The anti-inflammatory effect of SIRT3 underlying in oleanolic acid- (OLA-) prevented interleukin-1β- (IL-1β-) induced FLS dysfunction is then evaluated in vitro. Additionally, the molecular mechanisms of SIRT3 are assessed, and the interaction between SIRT3 and NF-κB is investigated. The data suggested that SIRT3 can be detected in human synovial tissues during OA, and OLA could elevate SIRT3 expression. OE-SIRT3 and OLA exhibited equal authenticity to repress inflammation and reverse oxidative stress changes in IL-1β-induced human FLS dysfunction. KD-SIRT3 was found to exacerbate inflammation and oxidative stress changes in human FLS. Furthermore, it was found that SIRT3 could directly bind with NF-κB, resulting in the suppression of NF-κB activation induced by IL-1β in human FLS, which then repressed synovial inflammation in OA. In general, the activation of SIRT3 by OLA inhibited synovial inflammation by suppressing the NF-κB signal pathway in FLS, and this suggested that SIRT3 is a potential target for OA synovitis therapy.

Highlights

Osteoarthritis (OA) is the most common joint degenerative disease, characterized by cartilage degradation, underlying bone remodeling, and synovial inflammation [1]
The results demonstrated that the absorption value of A450 increased with increasing concentrations of Oleanolic acid (OLA) at 24 h, 48 h, and 72 h (Figure 1(a))
This protein was focused on in this study, and it was found that OLA significantly increased the expression of sirtuin 3 (SIRT3) in Fibroblast-like synoviocytes (FLS) according to the result of the RT-PCR (Figure 1(b))

Summary

Introduction

Osteoarthritis (OA) is the most common joint degenerative disease, characterized by cartilage degradation, underlying bone remodeling, and synovial inflammation [1]. Many studies have explored the development mechanism of OA, including low-grade inflammation research, epigenetic research, DNA methylation, microRNA, long noncoding RNA, and circRNA research [2]. Synovial fluid (SF) biomarkers, such as CD14, CD163, and SF elastase, can predict knee OA progression. It is well documented that synovium can produce synovial fluid and nutrition for joint homeostasis, and its function is essential for physiological behaviors [5]. Fibroblast-like synoviocytes (FLS), the crucial resident cells in the synovium, constitute up to 75% of all cells in the synovium and maintain the synovial tissue extracellular matrix and synovial fluid homeostasis [6].

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