A LINC00341-mediated regulatory pathway supports chondrocyte survival and may prevent osteoarthritis progression

J Cell Biochem. 2019 Jun;120(6):10812-10820. doi: 10.1002/jcb.28372. Epub 2019 Jan 22.

Abstract

Osteoarthritis (OA) is the most common degenerative joint disease and results from progressive loss and destruction of articular cartilage and the underlying bone. The disease affects millions of people worldwide with an associated risk of mobility disability. However, the molecular basis underlying OA initiation and progression is not well understood and, currently, there is no effective intervention available to decelerate disease progression or restore degraded cartilage. We have found that lncRNA long intergenic nonprotein coding RNA 341 (LINC00341) is aberrantly downregulated in OA patient tissues and cultured OA chondrocytes. This is likely responsible for the increased apoptosis of chondrocytes and pathological destruction of cartilage. Further investigation has revealed that LINC00341 interacts with miR-141 to suppress its functional binding to the 3'-untranslated region of YY1-associated factor 2 (YAF2) messenger RNA. Aberrant downregulation of LINC00341 thus may ultimately lead to inhibition of the YAF2 protein, which has been implicated to be an antiapoptotic factor. Our study has revealed a new noncoding RNA-mediated regulatory network that highly likely protects chondrocytes by preventing apoptosis under normal conditions. The results will help further explore the molecular details pertaining to the progression of OA and stimulate efforts to develop effective therapies.

Keywords: YAF2 mRNA; chondrocytes; lncRNA LINC00341; molecular; osteoarthritis.

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis / genetics
  • Arthroplasty, Replacement, Hip / methods
  • Arthroplasty, Replacement, Knee / methods
  • Base Pairing
  • Base Sequence
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Cartilage, Articular / surgery
  • Cell Survival
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Disease Progression
  • Gene Expression Regulation
  • Genes, Reporter
  • Hip Joint / metabolism
  • Hip Joint / pathology
  • Hip Joint / surgery
  • Humans
  • Knee Joint / metabolism
  • Knee Joint / pathology
  • Knee Joint / surgery
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism
  • Osteoarthritis / genetics*
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Osteoarthritis / surgery
  • Primary Cell Culture
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Signal Transduction / genetics*

Substances

  • 3' Untranslated Regions
  • MIRN141 microRNA, human
  • MicroRNAs
  • Muscle Proteins
  • RNA, Long Noncoding
  • Repressor Proteins
  • YAF2 protein, human
  • long non-coding RNA LINC00341, human
  • Luciferases