Mushtaq T, Farquharson C, Seawright E, Ahmed S F
Department of Child Health, Royal Hospital for Sick Children, Yorkhill, Glasgow G3 8SJ, UK.
J Endocrinol. 2002 Dec;175(3):705-13. doi: 10.1677/joe.0.1750705.
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.
糖皮质激素（GC）在儿童中广泛使用，可能导致生长迟缓，部分原因是GC对生长板的直接作用。我们对ATDC5软骨细胞系进行了表征，该细胞系模拟了纵向骨生长的体内过程，以研究地塞米松（Dex）和泼尼松龙（Pred）在软骨细胞生命周期的两个关键时间点——软骨形成和终末分化过程中的作用。此外，我们研究了Dex暴露后恢复的可能性。在软骨形成过程中，10⁻⁸M、10⁻⁷M和10⁻⁶M的Dex和Pred暴露导致细胞数量显著平均减少（分别为28%对20%）、细胞增殖显著平均减少（分别为27%对24%）和蛋白聚糖合成显著平均减少（分别为47%对43%），并增加碱性磷酸酶（ALP）活性（分别为106%对62%），而细胞凋亡发生率未改变。在终末分化过程中，两种GC的作用均较小，尽管所有浓度的Dex均降低了凋亡细胞数量。为了评估追赶生长，细胞共孵育14天，其中包括在恢复期之前暴露于10⁻⁶M Dex 1天、3天、7天、10天或14天。仅暴露于Dex 1天，蛋白聚糖合成的恢复就受到不可逆损害。尽管细胞数量呈现类似模式，但仅在暴露14天后才出现显著损害。仅在暴露于Dex 10天后才注意到ALP活性的不可逆变化。总之，GC在软骨形成过程中具有最大作用；Dex比Pred更有效，暴露于Dex的细胞可恢复，但由于GC对特定软骨细胞表型的不同作用，这种恢复可能受到限制。
