The Influence of TGF-β3, EGF, and BGN on SOX9 and RUNX2 Expression in Human Chondrogenic Progenitor Cells

J Histochem Cytochem. 2019 Feb;67(2):117-127. doi: 10.1369/0022155418811645. Epub 2018 Nov 15.

Abstract

Osteoarthritis (OA) is the most common chronic joint disease and leads to the degradation of the extracellular matrix by an imbalance between anabolic and catabolic processes. TGF-β3 (transforming growth factor beta-3) and epidermal growth factor (EGF) influence the osteochondrogenic potential of chondrocytes. In this study, we compared the expression of mediators and receptors in the TGF-β3 and EGF pathways, as well as biglycan (BGN), in healthy and diseased chondrocytes. Furthermore, we used chondrogenic progenitor cells (CPCs) for in vitro stimulation and knockdown experiments to elucidate the effects of TGF-β3 and EGF on the chondrogenic potential. Our results demonstrate that the expression of TGF-beta receptor type-1 (TGFBRI) and epidermal growth factor receptor (EGFR) is altered in diseased chondrocytes as well as in CPCs. Moreover, TGF-β3 and EGF stimulation influenced the expression levels of BGN, SRY (sex determining region Y)-box 9 (SOX9), and Runt-related transcription factor 2 (RUNX2) in CPCs. Therefore, changes in TGFBRI and EGFR expression likely contribute to the degenerative and regenerative effects seen in late stages of OA.

Keywords: articular cartilage; chondrocytes; chondrogenesis; extracellular matrix.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biglycan / genetics*
  • Biomarkers / metabolism
  • Cell Differentiation
  • Chondrogenesis
  • Core Binding Factor Alpha 1 Subunit / genetics*
  • Epidermal Growth Factor / genetics*
  • Female
  • Gene Expression Regulation*
  • Humans
  • Male
  • SOX9 Transcription Factor / genetics*
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transforming Growth Factor beta3 / genetics*

Substances

  • Biglycan
  • Biomarkers
  • Core Binding Factor Alpha 1 Subunit
  • RUNX2 protein, human
  • SOX9 Transcription Factor
  • Transforming Growth Factor beta3
  • Epidermal Growth Factor