LncRNA SNHG1 alleviates IL-1β-induced osteoarthritis by inhibiting miR-16-5p-mediated p38 MAPK and NF-κB signaling pathways

Biosci Rep. 2019 Sep 6;39(9):BSR20191523. doi: 10.1042/BSR20191523. Print 2019 Sep 30.

Abstract

Long non-coding RNA (LncRNA) small nucleolar RNA host gene 1 (SNHG1) has been reported in the occurrence and development of several diseases, but its biological role and mechanism in osteoarthritis (OA) remain to be illuminated. In the present research, we aimed to investigate the effect of SNHG1 on IL-1β-induced OA and its molecular mechanism. Results revealed that SNHG1 decreased the expression of MMPs, ADAMTs, collagen, and aggrecan, and ameliorates IL-1β-induced metabolic dysfunction in normal human chondrocytes-keen. In addition, SNHG1 inhibited the expressions of pro-inflammatory cytokines in chondrocytes, including NO, PGE2, IL-6, TNF-α, i-NOS, and COX-2. Furthermore, luciferase reporter assay demonstrated that SNHG1 could directly interact with miR-16-5p and suppressed miR-16-5p expression and activity. What is more, miR-16-5p overexpression reversed SNHG1-inhibited aberrant catabolism and inflammation triggered by IL-1β stimulation. Finally, SNHG1 inhibits the expression of miR-16-5p-mediated factors involved in p38MAPK and NF-κB signaling pathways, including ERK1/2, p-p38 and p-p65. Taken together, the results of our studies illuminate that SNHG1 alleviates the inflammation of IL-1β-induced OA through the activation of miR-16-5p-mediated p38MAPK and NF-κB signaling pathway. It suggested that SNHG1 may serve as a potential target for OA diagnosis and treatment.

Keywords: NF-κB; Osteoarthritis; SNHG1; miR-16-5p; p38MAPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Gene Expression Regulation / genetics
  • Humans
  • Interleukin-1beta / pharmacology
  • MicroRNAs / genetics*
  • NF-kappa B / genetics
  • Osteoarthritis / chemically induced
  • Osteoarthritis / genetics*
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / genetics
  • Transcription Factor RelA / genetics
  • Tumor Necrosis Factor-alpha / genetics
  • p38 Mitogen-Activated Protein Kinases / genetics*

Substances

  • Interleukin-1beta
  • MIRN16 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RELA protein, human
  • RNA, Long Noncoding
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • long non-coding RNA SNHG1, human
  • p38 Mitogen-Activated Protein Kinases