The lncRNA, Nespas, Is Associated with Osteoarthritis Progression and Serves as a Potential New Prognostic Biomarker

Cartilage. 2019 Apr;10(2):148-156. doi: 10.1177/1947603517725566. Epub 2017 Aug 13.

Abstract

Introduction: In this article, we explored the hypothesis that the long noncoding RNA, Nespas, promotes osteoarthritis (OA) by supporting abnormal lipid metabolism in human chondrocytes.

Materials and methods: Human articular chondrocytes from osteoarthritis patients were used and expression level of Nespas were determined by real-time polymerase chain reaction. Introduction of Nespas and Nespas-associated genes/miRNAs were performed by using a lentiviral system. The effect of Nespas on mitochondrial function was determined by staining mitochondria and analyzing mitopotential and mitochondrial genes. Moreover, to identify the responsible molecules in Nespas-induced pathogenesis, profiling of peroxisomal genes and miRNAs were applied and interactome analysis was performed.

Results: Highly elevated levels of Nespas and Acyl-CoA synthetase 6 (ACSL6) were observed in OA patients. Both Nespas overexpression and ACSL6 upregulation into human chondrocytes induced typical OA characteristics, such as downregulation of type II collagen; upregulation of type I collagen, metalloproteinase 13, and caspase-1 and -3; and dysfunction of mitochondria and peroxisome. Co-expression of Nespas and ACSL6 siRNA reduced caspase-1 and -3 levels. Moreover, Nespas overexpression significantly suppressed levels of miR-291a-3p, -196a-5p, -23a-3p, -24-3p, and let-7a-5p, and these miRs are known to potentially target ACSL6 according to ingenuity pathway analysis. We also confirmed that these miRs were significantly suppressed in human OA chondrocytes. Overexpression of miR-291a-3p, -196a-5p, -23a-3p, -24-3p, or let-7a-5p in the presence of Nespas suppressed levels of ACSL6, caspase-1 and -3.

Discussion: Overall, we suggest that elevated Nespas level in OA are associated with OA pathogenesis by suppressing miRs targeting ACSL6 and subsequent ACSL6 upregulation.

Keywords: ACSL6; Nespas; human articular chondrocytes; osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Cell Culture Techniques
  • Chondrocytes / metabolism*
  • Chromogranins / genetics*
  • Coenzyme A Ligases / metabolism*
  • Disease Progression
  • Down-Regulation
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • Humans
  • MicroRNAs
  • Osteoarthritis / genetics*
  • Prognosis
  • RNA, Long Noncoding / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Up-Regulation

Substances

  • Biomarkers
  • Chromogranins
  • MicroRNAs
  • RNA, Long Noncoding
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs
  • Coenzyme A Ligases
  • ACSL6 protein, human