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Interleukin-34 overexpression mediated through tumor necrosis factor-alpha reflects severity of synovitis in knee osteoarthritis.

ABSTRACT: This study aimed to investigate whether interleukin-34 (IL-34) mRNA expression is aberrant and modulated by tumor necrosis factor-alpha (TNF-?) in knee osteoarthritis (OA) fibroblast-like synoviocytes (FLS) and determine associations of IL-34 mRNA and protein in the systemic and local joint environments with severity of knee OA synovitis. Transcriptional and translational IL-34 levels in FLS, synovium, synovial fluid, and plasma of knee OA were determined using real-time polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. Relative mRNA expressions of NF-?B signaling molecules were further measured. In knee OA FLS stimulated with TNF-?, IL-34 mRNA expression was significantly up-regulated in a time-dependent manner. In knee OA synovium with severe synovitis, increased IL-34 mRNA expression was directly associated with IL-6, I?B, NF-?B, and MMP-13, in addition to knee OA FLS. Immunostaining score of IL-34 was considerably greater in knee OA synovium with severe synovitis than that in those with mild and no synovitis. Increments in joint fluid and plasma IL-34 levels in knee OA patients with severe synovitis were closely related to its mRNA and protein expressions in knee OA synovium. Transcriptional and translational expressions of IL-34 were positively correlated with synovitis severity. Collectively, IL-34 overexpression would reflect synovitis severity in knee OA.

SUBMITTER: Udomsinprasert W

PROVIDER: S-EPMC7224362 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Interleukin-34 overexpression mediated through tumor necrosis factor-alpha reflects severity of synovitis in knee osteoarthritis.

Udomsinprasert Wanvisa W Jinawath Artit A Teerawattanapong Nipaporn N Honsawek Sittisak S

Scientific reports 20200514 1

This study aimed to investigate whether interleukin-34 (IL-34) mRNA expression is aberrant and modulated by tumor necrosis factor-alpha (TNF-α) in knee osteoarthritis (OA) fibroblast-like synoviocytes (FLS) and determine associations of IL-34 mRNA and protein in the systemic and local joint environments with severity of knee OA synovitis. Transcriptional and translational IL-34 levels in FLS, synovium, synovial fluid, and plasma of knee OA were determined using real-time polymerase chain reactio ...[more]

PMID: 32409720

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Project description:Background Osteoarthritis (OA) is one of the costliest and most disabling forms of arthritis, and it poses a major public health burden; however, its detailed etiology, pathophysiology, and metabolism remain unclear. Therefore, the purpose of this study was to investigate the key plasma metabolites and metabolic pathways, especially focusing on radiographic OA severity and synovitis, from a large sample cohort study. Methods We recruited 596 female volunteers who participated in the Iwaki Health Promotion Project in 2017. Standing anterior-posterior radiographs of the knee were classified by the Kellgren-Lawrence (KL) grade. Radiographic OA was defined as a KL grade of ≥ 2. Individual effusion-synovitis was scored according to the Whole-Organ Magnetic Resonance Imaging Scoring System. Blood samples were collected, and metabolites were extracted from the plasma. Metabolome analysis was performed using capillary electrophoresis time-of-flight mass spectrometry. To investigate the relationships among metabolites, the KL grade, and effusion-synovitis scores, partial least squares with rank order of groups (PLS-ROG) analyses were performed. Results Among the 82 metabolites examined in this assay, PLS-ROG analysis identified 42 metabolites that correlated with OA severity. A subsequent metabolite set enrichment analysis using the significant metabolites showed the urea cycle and tricarboxylic acid cycle as key metabolic pathways. Moreover, further PLS-ROG analysis identified cystine (p = 0.009), uric acid (p = 0.024), and tyrosine (p = 0.048) as common metabolites associated with both OA severity and effusion-synovitis. Receiver operating characteristic analyses showed that cystine levels were moderately associated with radiographic OA (p < 0.001, area under the curve 0.714, odds ratio 3.7). Conclusion Large sample metabolome analyses revealed that cystine, an amino acid associated with antioxidant activity and glutamate homeostasis, might be a potential metabolic biomarker for radiographic osteoarthritis and early phase synovitis. Supplementary Information The online version contains supplementary material available at 10.1186/s13075-022-02830-w.

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Interleukin-34 overexpression mediated through tumor necrosis factor-alpha reflects severity of synovitis in knee osteoarthritis.

Publications

Interleukin-34 overexpression mediated through tumor necrosis factor-alpha reflects severity of synovitis in knee osteoarthritis.

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