Endocrine Abstracts (2001) 2 P5

The effect of Glucocorticoids on growth plate chondrocyte proliferation and differentiation

T Mushtaq1,2, E Seawright2, C Farquharson2 & SF Ahmed1

1Dept of Child Health, Royal Hospital for Sick Children, Yorkhill, Glasgow; 2Dept of Integrative Biology, Roslin Institute, Edinburgh.

Background: Glucocorticoid (GC) induced growth retardation is partly due to effects on the growth plate but may vary depending on the pattern of GC exposure.

Aims: To compare the effects of dexamethasone (Dex) and prednisolone (Pred) and timing of GC exposure on chondrocyte proliferation and terminal differentiation on the ATDC5 murine chondrocyte cell line.

Methods: The cell line was fully characterized by assessing marker gene expression. The GC was added at either Day 0(D0) or Day 4 (D4) at a concentration of 10-6,10-7,10-8 M. Alkaline phosphatase (ALP), protein and proteoglycan synthesis (PG) concentrations were determined at D4 and D9, respectively.

Results: RT-PCR indicated that chondrogenesis occurred during D0-4, and terminal differentiation during D4-9. Both GCs (10-6 and 10-7 M) decreased (p<0.05) PG synthesis at day 9. Total cellular protein (mg) at D4 of 10-6 and 10-7 M Dex was 0.25 (SD 0.12) and 0.36 (SD 0.07) respectively, which was significantly lower than the control cultures [0.69 (SD 0.14)]. This trend was also noted at D9. Pred significantly reduced cell number at D4 [10-6 M 0.18 (SD 0.10)]; control 0.64 (SD 0.19) and D9 [10-6 M, 0.33 (SD 0.14); control, 0.54 (SD 0.08)]. Mean ALP (nm/mg protein> a marker of terminal differentiation, was elevated at D4 Dex 10-6 M [3136 (SD 924)] and 10-7 M [2266 (SD 477)] compared to control [1106 (SD 122)]. ALP at D4 and D9 was only elevated at Pred concentrations of 10-6 M. These GC effects on protein and ALP were more pronounced on D4 compared to D9.

Conclusion: The ATDC5 provides a model to study the effects of drugs on different maturational phases of chondrocyte differentiation. GC reduce chondrocyte proliferation and stimulate terminal differentiation. These effects are more pronounced during the chondrogenesis period and were observed at a lower concentration of Dex than Pred.

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