Chondrocyte p21(WAF1/CIP1) Expression Is Increased by Dexamethasone but Does Not Contribute to Dexamethasone-Induced Growth Retardation In Vivo

H. C. Owen, S. F. Ahmed, C. Farquharson

Research output: Contribution to journalArticlepeer-review

Abstract

It has been shown that cell cycle genes play an important role in the coordination of chondrocyte proliferation and differentiation. The inhibitory effects of glucocorticoids (GCs) on chondrocyte proliferation are consistent with GCs disrupting cell cycle progression and promoting cell cycle exit. Cyclin-dependent kinase inhibitors (CDKIs) force cells to exit the cell cycle and differentiate, and studies have shown that expression of the CDKI p21CIP1/WAF1 is increased in terminally differentiated cells. In this study, p21 mRNA and protein expression was increased during chondrocyte differentiation and after exposure to dexamethasone (Dex, 10−6 M) in murine chondrogenic ATDC5 cells. In 4-week-old mice lacking a functional p21 gene, Dex caused a reduction in body weight compared to saline control null mice, but this was consistent with the reduction in body weight observed in Dex-treated wild-type littermates. In addition, p21 ablation had no effect on the reduction in width of the growth plate or reduced mineral apposition rate in Dex-treated mice. However, an alteration in growth rate and epiphyseal structure is evident when comparing p21−/− and wild-type mice. These findings suggest that p21 does not directly contribute to GC-induced growth retardation in vivo but is involved in the maintenance of the growth plate.
Original languageEnglish
Pages (from-to)326-334
Number of pages9
JournalCalcified Tissue International
Volume85
Issue number4
DOIs
Publication statusPublished - Oct 2009

Keywords

  • Animals
  • Body Weight
  • Bone Density
  • Cell Cycle
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Chondrocytes
  • Cyclin-Dependent Kinase Inhibitor p21
  • Dexamethasone
  • Disease Models, Animal
  • Female
  • Glucocorticoids
  • Growth Disorders
  • Mice
  • Mice, Knockout

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