Gulp1 regulates chondrocyte growth arrest and differentiation via the TGF-β/SMAD2/3 pathway

FEBS Lett. 2024 Apr;598(8):935-944. doi: 10.1002/1873-3468.14862. Epub 2024 Mar 29.

Abstract

Chondrocyte differentiation is crucial for cartilage formation. However, the complex processes and mechanisms coordinating chondrocyte proliferation and differentiation remain incompletely understood. Here, we report a novel function of the adaptor protein Gulp1 in chondrocyte differentiation. Gulp1 expression is upregulated during chondrogenic differentiation. Gulp1 knockdown in chondrogenic ATDC5 cells reduces the expression of chondrogenic and hypertrophic marker genes during differentiation. Furthermore, Gulp1 knockdown impairs cell growth arrest during chondrocyte differentiation and reduces the expression of the cyclin-dependent kinase inhibitor p21. The activation of the TGF-β/SMAD2/3 pathway, which is associated with p21 expression in chondrocytes, is impaired in Gulp1 knockdown cells. Collectively, these results demonstrate that Gulp1 contributes to cell growth arrest and chondrocyte differentiation by modulating the TGF-β/SMAD2/3 pathway.

Keywords: Gulp1; cell growth arrest; chondrocyte; differentiation; p21.

Publication types

  • Research Support, Non-U.S. Gov't
  • Letter

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Cycle Checkpoints / genetics
  • Cell Differentiation*
  • Cell Line
  • Cell Proliferation
  • Chondrocytes* / cytology
  • Chondrocytes* / metabolism
  • Chondrogenesis* / genetics
  • Cyclin-Dependent Kinase Inhibitor p21* / genetics
  • Cyclin-Dependent Kinase Inhibitor p21* / metabolism
  • Gene Knockdown Techniques
  • Mice
  • Signal Transduction*
  • Smad2 Protein* / genetics
  • Smad2 Protein* / metabolism
  • Smad3 Protein* / genetics
  • Smad3 Protein* / metabolism
  • Transforming Growth Factor beta* / metabolism

Substances

  • Smad2 Protein
  • Smad3 Protein
  • Transforming Growth Factor beta
  • Smad2 protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Smad3 protein, mouse
  • Adaptor Proteins, Signal Transducing