LncRNA-CIR promotes articular cartilage degeneration in osteoarthritis by regulating autophagy

Biochem Biophys Res Commun. 2018 Nov 2;505(3):692-698. doi: 10.1016/j.bbrc.2018.09.163. Epub 2018 Oct 3.

Abstract

Osteoarthritis (OA) is a common joint disease that is regarded as a local inflammatory response caused by joint instability and accompanied by the progressive degeneration of articular cartilage. However, the molecular mechanisms involved in the maintenance of articular cartilage remain a subject of debate and research. This study aims to analyze the roles of long noncoding RNA (lncRNA)CIR and autophagy in cartilages and determine their overall contribution to the degradation of extracellular matrix. Patients with OA possessed high levels of lncRNA-CIR and MMP3 and low level of COL2A1. The levels of autophagy-related proteins, including LC3BI/II and beclin-1, increased from 12 h to 48 h. The use of si-lncRNA-CIR reversed the trend compared with that in the OA group. The negative effect of lncRNA-CIR was assessed in vivo by establishing a model of surgically induced OA. Moreover, si-lncRNA-CIR-treated joints exhibited fewer OA changes than saline-treated joints. Results were confirmed by histopathological grading of the models by using the Osteoarthritis Research Society International Scoring System and the outcomes of immunohistochemistry for LC3B-II and MMP-3. Overall, lncRNA-CIR played a negative role in the OA process by activating autophagy.

Keywords: Autophagy; Cartilage degeneration; Osteoarthritis; lncRNA-CIR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Autophagy / genetics*
  • Beclin-1 / metabolism
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Cells, Cultured
  • Chondrocytes / metabolism
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Osteoarthritis / genetics*
  • Osteoarthritis / metabolism
  • RNA, Long Noncoding / genetics*
  • Rats, Sprague-Dawley

Substances

  • Beclin-1
  • COL2A1 protein, human
  • Collagen Type II
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • RNA, Long Noncoding
  • Matrix Metalloproteinase 13