CPEB1 Expression Correlates with Severity of Posttraumatic Ankle Osteoarthritis and Aggravates Catabolic Effect of IL-1β on Chondrocytes

Inflammation. 2019 Apr;42(2):628-636. doi: 10.1007/s10753-018-0920-6.

Abstract

Most cases of posttraumatic ankle osteoarthritis (PTAOA) represent a sequela of ankle fractures. The cytoplasmic polyadenylation element-binding protein 1 (CPEB1) is an RNA binding protein that controls protein expression. Here, we report the previously unappreciated association of CPEB1 with PTAOA. We found that CPEB1 was upregulated in articular cartilage from patients with PTAOA. Additionally, its expression level positively correlated with disease severity. In human primary chondrocytes cultured in vitro, CPEB1 was upregulated when treated with pro-inflammatory cytokines, i.e., IL-1β and TNF-α, suggesting that the observed CPEB1 upregulation in articular cartilage of PTAOA patients may be attributed to local inflammatory milieu. Functionally, CPEB1 overexpression aggravated the catabolic effect of IL-1β on chondrocytes in vitro, and vice versa, its knockdown reduced this effect, together implying a detrimental role of CPEB1 involved in OA progression. In sum, our study identifies CPEB1 as a potential regulator of disease progression of PTAOA.

Keywords: CPEB1; IL-1β; catabolism; chondrocyte; correlation; posttraumatic ankle osteoarthritis.

MeSH terms

  • Ankle
  • Cartilage, Articular
  • Cells, Cultured
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Disease Progression
  • Female
  • Humans
  • Inflammation Mediators
  • Interleukin-1beta / pharmacology*
  • Male
  • Middle Aged
  • Osteoarthritis / pathology*
  • Transcription Factors / drug effects
  • Transcription Factors / metabolism*
  • Transcription Factors / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation
  • Wounds and Injuries
  • mRNA Cleavage and Polyadenylation Factors / drug effects
  • mRNA Cleavage and Polyadenylation Factors / metabolism*
  • mRNA Cleavage and Polyadenylation Factors / pharmacology

Substances

  • CPEB1 protein, human
  • Inflammation Mediators
  • Interleukin-1beta
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • mRNA Cleavage and Polyadenylation Factors