Catch-up growth after dexamethasone withdrawal occurs in cultured postnatal rat metatarsal bones
Catch-up growth after dexamethasone withdrawal occurs in cultured postnatal rat metatarsal bones
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DOI：
10.1677/joe-09-0307
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Savendahl, Lars
中科院分区：
文献类型：
--
作者：
Chagin, Andrei S.;Karimian, Elham;Savendahl, Lars
暴露于全身糖皮质激素的儿童通常表现出生长迟缓，在停止治疗后，许多患者但不是所有患者都会出现追赶生长。追赶生长的发育调控和潜在的细胞机制尚不完全清楚。为了阐明这个问题，我们建立了一个追赶生长的体外模型。在这里，我们提出了一种长期培养胎儿(E20)和出生后(P8)大鼠跖骨的方案，使我们能够在不受任何系统性因素影响的情况下，在体外表征追赶生长的现象。IGF1(100 ng/ml)对胎儿和出生后骨骼的生长有促进作用，而地塞米松(Dexa)对骨骼生长有抑制作用，证实了该模型的相关性。我们发现，追赶生长的能力仅限于出生后的骨骼。在出生后骨骼暴露于地塞米松7天或12天后，追赶生长发生，但在更长时间的暴露(19天)后不发生。在4个月培养期末进行评估时，不完全追赶生长会导致骨长度受损。虽然接触地塞米松与软骨细胞增殖和分化减少有关，但追赶生长只与细胞增殖增加有关。我们得出结论，地塞米松治疗后的追赶生长现象是生长板固有的，主要是通过上调软骨细胞的增殖来调节的。内分泌学杂志(2010)204，21-29
Children exposed to systemic glucocorticoids often exhibit growth retardation and after the cessation of therapy catch-up growth occurs in many, but not all patients. The developmental regulation and underlying cellular mechanisms of catch-up growth are not fully understood. To clarify this issue, we established an in vitro model of catch-up growth. Here we present a protocol for the long-term culture (up to 160 days) of fetal (E20) as well as postnatal (P8) rat metatarsal bones which allowed us to characterize ex vivo the phenomenon of catch-up growth without any influence by systemic factors. The relevance of the model was confirmed by the demonstration that the growth of fetal and postnatal bones were stimulated by IGF1 (100 ng/ml) and inhibited by dexamethasone (Dexa; 1 mu M). We found that the capacity to undergo catch-up growth was restricted to postnatal bones. Catch-up growth occurred after postnatal bones had been exposed to Dexa for 7 or 12 days but not after a more prolonged exposure (19 days). Incomplete catch-up growth resulted in compromised bone length when assessed at the end of the 4-month period of culture. While exposure to Dexa was associated with decreased chondrocyte proliferation and differentiation, catch-up growth was only associated with increased cell proliferation. We conclude that the phenomenon of catch-up growth after Dexa treatment is intrinsic to the growth plate and primarily mediated by an upregulation of chondrocyte proliferation. Journal of Endocrinology (2010) 204, 21-29