Glucocorticoid effects on chondrogenesis, differentiation and apoptosis in the murine ATDC5 chondrocyte cell line

T Mushtaq, C Farquharson, E Seawright, S F Ahmed

Research output: Contribution to journalArticlepeer-review

Abstract

Glucocorticoids (GC) are used extensively in children and may cause growth retardation, which is in part due to the direct effects of GC on the growth plate. We characterised the ATDC5 chondrocyte cell line, which mimics the in vivo process of longitudinal bone growth, to examine the effects of dexamethasone (Dex) and prednisolone (Pred) during two key time points in the chondrocyte life cycle - chondrogenesis and terminal differentiation. Additionally, we studied the potential for recovery following Dex exposure. During chondrogenesis, Dex and Pred exposure at 10(-8) M, 10(-7) M and 10(-6) M resulted in a significant mean reduction in cell number (28% vs 20%), cell proliferation (27% vs 24%) and proteoglycan synthesis (47% vs 43%) and increased alkaline phosphatase (ALP) activity (106% vs 62%), whereas the incidence of apoptosis was unaltered. Minimal effects were noted during terminal differentiation with both GC although all concentrations of Dex lowered apoptotic cell number. To assess catch-up growth the cells were incubated for a total of 14 days which included 1, 3, 7, 10 or 14 days exposure to 10(-6) M Dex, prior to the recovery period. Recovery of proteoglycan synthesis was irreversibly impaired following just one day exposure to Dex. Although cell number showed a similar pattern, significant impairment was only achieved following 14 days exposure. Irreversible changes in ALP activity were only noticed following 10 days exposure to Dex. In conclusion, GC have maximal effects during chondrogenesis; Dex is more potent than Pred and cells exposed to Dex recover but this may be restricted due to differential effects of GC on specific chondrocyte phenotypes.
Original languageEnglish
Pages (from-to)705-13
Number of pages9
JournalJournal of Endocrinology
Volume175
Issue number3
DOIs
Publication statusPublished - Dec 2002

Keywords

  • Animals
  • Apoptosis
  • Cell Count
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Chondrocytes
  • Chondrogenesis
  • Collagen Type II
  • Collagen Type X
  • Dexamethasone
  • Glucocorticoids
  • Mice
  • Prednisolone
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors

Fingerprint

Dive into the research topics of 'Glucocorticoid effects on chondrogenesis, differentiation and apoptosis in the murine ATDC5 chondrocyte cell line'. Together they form a unique fingerprint.

Cite this