title: MicroRNA-26a-5p regulates the expression of inducible nitric oxide synthase via activation of NF-κB pathway in human osteoarthritis chondrocytes.
abstract: Inducible nitric oxide synthase (iNOS) expression is associated with the pathogenesis of osteoarthritis (OA). This study was undertaken to investigate whether interleukin-1β (IL-1β)-mediated induction of iNOS can be regulated by microRNA-26a-5p (hsa-miR-26a-5p) in OA. Bioinformatics approaches show that 3'UTR of iNOS mRNA contained the 'seed-matched-sequence' for hsa-miR-26a-5p. IL-1β-induced expression of iNOS correlated with the down-regulation of miR-26a-5p in human OA chondrocytes. hsa-miR-26a-5p directly suppressed the luciferase activity of 3'UTR-iNOS reporter clone. Transfection with pre-miR-26a-5p induced marked silencing of iNOS expression. Activation of NF-κB pathway down-regulated the expression of hsa-miR-26a-5p and induced iNOS expression. In short, this is the first report that shows hsa-miR-26a-5p is a direct regulator of iNOS expression in human chondrocytes. hsa-miR-26a-5p may be an important regulator of human cartilage homeostasis and a new target for OA therapy.
authors: Department of Medical Biochemistry, College of Medicine, Qassim University, Buraidah, Saudi Arabia. Electronic address: zafarrasheed@qumed.edu.sa.
authors: Zafar
authors: Z
authors: Rasheed
authors: Department of Dermatology, College of Medicine, Qassim University, Saudi Arabia.
authors: Hani A
authors: HA
authors: Al-Shobaili
authors: Department of Medical Biochemistry, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
authors: Naila
authors: N
authors: Rasheed
authors: Stem Cell Unit, Department of Anatomy College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors: Amer
authors: A
authors: Mahmood
authors: Institute of Genetics, School of Biology, Queens Medical Center, Medical School, Nottingham, UK.
authors: Mohammed Imran
authors: MI
authors: Khan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019295:Computational Biology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D053583:Interleukin-1beta; D035683:MicroRNAs; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; C528163:MIRN26 microRNA, human
keywords: Chondrocytes; IL-1β; NF-κB; Osteoarthritis; iNOS; microRNA 26a-5p