Overexpression of long non-coding RNA AP001505.9 inhibits human hyaline chondrocyte dedifferentiation

Aging (Albany NY). 2021 Apr 4;13(8):11433-11454. doi: 10.18632/aging.202833. Epub 2021 Apr 4.

Abstract

Autologous chondrocyte implantation (ACI) is an effective method for treating chronic articular cartilage injury and degeneration; however, it requires large numbers of hyaline chondrocytes, and human hyaline chondrocytes often undergo dedifferentiation in vitro. Moreover, although long non-coding RNAs (lncRNAs) regulate gene expression in many pathological and physiological processes, their role in human hyaline chondrocyte dedifferentiation remains unclear. Here, we examined lncRNA and mRNA expression profiles in human hyaline chondrocyte dedifferentiation using microarray analysis. Among the many lncRNAs and mRNAs that showed differential expression, lncRNA AP001505.9 (ENST00000569966) was significantly downregulated in chondrocytes after dedifferentiation. We next performed gene ontology, pathway, and CNC (coding-non-coding gene co-expression) analyses to investigate potential regulatory mechanisms for AP001505.9. Pellet cultures were then used to redifferentiate dedifferentiated chondrocytes, and AP001505.9 expression was upregulated after redifferentiation. Finally, both in vitro and in vivo experiments demonstrated that AP001505.9 overexpression inhibited dedifferentiation of chondrocytes. This study characterizes lncRNA expression profiles in human hyaline chondrocyte dedifferentiation, thereby identifying new potential mechanisms of chondrocyte dedifferentiation worthy of further investigation.

Keywords: autologous chondrocyte implantation; dedifferentiation; hyaline chondrocyte; long non-coding RNA AP001505.9; osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cartilage, Articular / cytology
  • Cartilage, Articular / growth & development*
  • Cartilage, Articular / metabolism
  • Cell Dedifferentiation / genetics*
  • Cells, Cultured
  • Chondrocytes / physiology*
  • Chondrogenesis / genetics*
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Primary Cell Culture
  • RNA, Long Noncoding / metabolism*

Substances

  • RNA, Long Noncoding