Regulation of the Inflammatory Synovial Fibroblast Phenotype by Metastasis‐Associated Lung Adenocarcinoma Transcript 1 Long Noncoding RNA in Obese Patients With Osteoarthritis.
Objective: To identify long noncoding RNAs (lncRNAs) associated with the inflammatory phenotype of synovial fibroblasts from obese patients with osteoarthritis (OA), and to explore the expression and function of these lncRNAs. Methods: Synovium was collected from normal‐weight patients with hip frac...
| Publicado en: | Arthritis & Rheumatology Vol. 72; no. 4; pp. 609 - 620 |
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| Autores principales: | , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Apr2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=142479670&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 142479670 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23265191 H06R jtl: Arthritis & Rheumatology issn: 23265191 maglogo: N pubinfo: dt: Apr2020 vid: 72 iid: 4 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 142479670 142479670 145824631 142479670 10.1002/art.41158 142479670 ppf: 609 ppct: 11 formats: tig: atl: Regulation of the Inflammatory Synovial Fibroblast Phenotype by Metastasis‐Associated Lung Adenocarcinoma Transcript 1 Long Noncoding RNA in Obese Patients With Osteoarthritis. aug: au: Nanus, Dominika E. Wijesinghe, Susanne N. Pearson, Mark J. Hadjicharalambous, Marina R. Rosser, Alex Davis, Edward T. Lindsay, Mark A. Jones, Simon W. affil: University of Birmingham, Birmingham, UK sug: subj: Osteoarthritis Obesity Synovial Membrane Fibroblasts RNA Gene Expression Human Phenotype Lung Neoplasms Adenocarcinoma Neoplasm Metastasis ab: Objective: To identify long noncoding RNAs (lncRNAs) associated with the inflammatory phenotype of synovial fibroblasts from obese patients with osteoarthritis (OA), and to explore the expression and function of these lncRNAs. Methods: Synovium was collected from normal‐weight patients with hip fracture (non‐OA; n = 6) and from normal‐weight (n = 8) and obese (n = 8) patients with hip OA. Expression of RNA was determined by RNA‐sequencing and quantitative reverse transcription–polymerase chain reaction. Knockdown of lncRNA was performed using LNA‐based GapmeRs. Synovial fibroblast cytokine production was measured by enzyme‐linked immunosorbent assay. Results: Synovial fibroblasts from obese patients with OA secreted greater levels of interleukin‐6 (IL‐6) (mean ± SEM 162 ± 21 pg/ml; P < 0.001) and CXCL8 (262 ± 67 pg/ml; P < 0.05) compared to fibroblasts from normal‐weight patients with OA (IL‐6, 51 ± 4 pg/ml; CXCL8, 78 ± 11 pg/ml) or non‐OA patients (IL‐6, 35 ± 3 pg/ml; CXCL8, 56 ± 6 pg/ml) (n = 6 patients per group). RNA‐sequencing revealed that fibroblasts from obese OA patients exhibited an inflammatory transcriptome, with increased expression of proinflammatory messenger RNAs (mRNAs) as compared to that in fibroblasts from normal‐weight OA or non‐OA patients (>2‐fold change, P < 0.05; n = 4 patients per group). A total of 19 lncRNAs were differentially expressed between normal‐weight OA and non‐OA patient fibroblasts, and a further 19 lncRNAs were differentially expressed in fibroblasts from obese OA patients compared to normal‐weight OA patients (>2‐fold change, P < 0.05 for each), which included the lncRNA for metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1 was rapidly induced upon stimulation of OA synovial fibroblasts with proinflammatory cytokines, and was up‐regulated in the synovium from obese OA patients as compared to normal‐weight OA patients (1.6‐fold change, P < 0.001) or non‐OA patients (6‐fold change, P < 0.001). MALAT1 knockdown in OA synovial fibroblasts (n = 4 patients) decreased the levels of mRNA expression and protein secretion of CXCL8 (>1.5‐fold change, P < 0.01), whereas it increased expression of mRNAs for TRIM6 (>2‐fold change, P < 0.01), IL7R (<2‐fold change, P < 0.01), HIST1H1C (>1.5‐fold change, P < 0.001), and MAML3 (>1.5‐fold change, P < 0.001). In addition, MALAT1 knockdown inhibited the proliferation of synovial fibroblasts from obese patients with OA. Conclusion: Synovial fibroblasts from obese patients with hip OA exhibit an inflammatory phenotype. MALAT1 lncRNA may mediate joint inflammation in obese OA patients. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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