FGF23 and SOX9 expression in haemophilic cartilage: In vitro studies of the effects of iron

Haemophilia. 2022 Nov;28(6):1062-1068. doi: 10.1111/hae.14623. Epub 2022 Jul 8.

Abstract

Introduction: Clarifying the links between iron and FGF23, SOX9 expression in chondrocytes would be helpful for comprehending articular cartilage degradation pathogenesis in blood-induced arthritis and exploring new protective methods.

Aim: The purpose of this study was to determine iron regulation of fibroblast growth factor 23 (FGF23) and SRY-box 9 (SOX9) in human chondrocytes, an area which is unexplored in blood-induced arthritis cartilage degradation pathogenesis.

Methods: Expression of FGF23, SOX9, MMP13 and collagen Ⅱ in articular cartilage of patients with osteoarthritis (OA) or haemophilic arthritis (HA) was determined by western blot (WB). Iron-induced FGF23 and SOX9 mRNA and protein expression in primary human normal chondrocyte cells (HUM-iCell-s018) was quantified by qRT-PCR and WB, respectively.

Results: We found that compared with OA patients, the expression of FGF23, MMP13 in articular cartilage of patients with HA was up-regulated, while the expression of SOX9, collagen Ⅱ was down-regulated. Iron-induced FGF23 and suppressed SOX9 expression in chondrocytes in a dose-dependent manner.

Conclusions: These findings demonstrated that iron was involved in hemophilic cartilage lesion directly via changing cartilage phenotype through regulation of FGF23 and SOX9 expression in chondrocytes.

Keywords: FGF23; SOX9; chondrocyte; haemophilic arthritis; osteoarthritis.

MeSH terms

  • Cartilage, Articular* / metabolism
  • Cells, Cultured
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Collagen / metabolism
  • Humans
  • Iron / metabolism
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 13 / pharmacology
  • Osteoarthritis* / genetics
  • Osteoarthritis* / pathology
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism
  • SOX9 Transcription Factor / pharmacology

Substances

  • Collagen
  • Iron
  • Matrix Metalloproteinase 13
  • SOX9 protein, human
  • SOX9 Transcription Factor
  • FGF23 protein, human