ReferenceID 5884
Oleanolic Acid Decreases IL-1 β-Induced Activation of Fibroblast-Like Synoviocytes via the SIRT3-NF- κ B Axis in Osteoarthritis
Oxid Med Cell Longev
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 secreto
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Record Fields
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- Reference Id
- 5884
- Evidence Id
- 22474
- Core Evidence Id
- 22474
- Source Reference Id
- 5038
- Herb2 Reference Id
- HBREF005835
- Subject Paper Key
- HBIN037940_33062145
- Pubmed Id
- 33062145
- Doi
- 10.1155/2020/7517219
- Paper Title
- Oleanolic Acid Decreases IL-1 β-Induced Activation of Fibroblast-Like Synoviocytes via the SIRT3-NF- κ B Axis in Osteoarthritis
- Paper 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-1beta- (IL-1beta-) induced FLS dysfunction is then evaluated in vitro. Additionally, the molecular mechanisms of SIRT3 are assessed, and the interaction between SIRT3 and NF-kappaB 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-1beta-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-kappaB, resulting in the suppression of NF-kappaB activation induced by IL-1beta 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-kappaB signal pathway in FLS, and this suggested that SIRT3 is a potential target for OA synovitis therapy.
- Journal
- Oxid Med Cell Longev
- Publish Year
- 2020
- Experiment Subject
- human
- Experiment Type
- Cell Experiment
- Phenotype Related
- Osteoarthritis; Chronic Degenerative Joint Disease; Oa Synovitis; Fls Dysfunction; Synovial Inflammation
- Paper Title Cn
- Paper Title En
- Oleanolic Acid Decreases IL-1 β-Induced Activation of Fibroblast-Like Synoviocytes via the SIRT3-NF- κ B Axis in Osteoarthritis
- Bilingual Status
- semi_complete