Effects of high-dose all-trans retinoic acid on longitudinal bone growth of young rats

IF 1.6 4区 医学 Q4 CELL BIOLOGY Growth Hormone & Igf Research Pub Date : 2022-02-01 DOI:10.1016/j.ghir.2022.101446
Qin Shen , Xia Wang , Haodi Bai , Xin Tan , Xing Liu
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引用次数: 4

Abstract

Objective

The signaling axis consisting of GH-IGF1-IGFBP3 is the primary signal taht acts prepubertally to influence height development. Growth plate thinning and even premature closure have been reported in children with tumors treated with retinoid chemotherapy, resulting in long bone dysplasia. Growth failure may occur despite received GH treatment, but the reason is unknown. This study investigate the effect of high-dose all-trans retinoic acid (ATRA) on the development of long bones in growing SD rats.

Methods

A total of 20 three-week-old male SD rats were randomly divided into a control group and an experimental group (n = 10). Rats were treated by gavage with or without high-dose ATRA for 10 days. The body weights of the rats were recorded daily. At the end of the experiment, we measured the length of nose-tail and tibia, stained the tibia and liver for pathological tissue and RT-PCR reaction, and measured the levels of serum GH, IGF1 and IGFBP3, and so on.

Results

Compared with controls, experimental rats exhibited reduced body weight and shortened nasal-tail and radial tibial length. Cyp26b1 enzyme activity in the liver was elevated, and histopathological staining revealed that the cartilaginous epiphyseal plate was narrowed, the medullary cavity of trabecular bone was sparse, the number of trabecular bones was decreased, trabecular separation was increased, bone marrow mineralization was enhanced, osteoclastic activity was increased, and circulating GH-IGF1-IGFBP3 levels were decreased. However, RT-PCR reaction results of localized proximal tibiae showed upregulation of IGF1 and downregulation of IGFBP3.

Conclusions

High-dose ATRA intake over a short period of time can reduce GH-IGF1-IGFBP3 levels, affect cartilage and bone homeostasis, and inhibit bone growth in developing animals.

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大剂量全反式维甲酸对幼鼠纵向骨生长的影响
目的GH-IGF1-IGFBP3信号轴是青春期前影响身高发育的主要信号。有报道称,在接受类维甲酸化疗的儿童肿瘤中,生长板变薄甚至过早闭合,导致长骨发育不良。尽管接受生长激素治疗,仍可能发生生长衰竭,但原因尚不清楚。本研究探讨了大剂量全反式维甲酸(ATRA)对生长SD大鼠长骨发育的影响。方法选用3周龄雄性SD大鼠20只,随机分为对照组和试验组(n = 10)。大鼠分别给予或不给予高剂量ATRA灌胃10 d。每天记录大鼠体重。实验结束后测量鼻尾和胫骨长度,对胫骨和肝脏进行病理组织染色和RT-PCR反应,测定血清GH、IGF1、IGFBP3水平等。结果与对照组相比,实验组大鼠体重减轻,鼻尾和桡胫长度缩短。肝脏Cyp26b1酶活性升高,组织病理学染色显示软骨骺板变窄,骨小梁髓腔稀疏,骨小梁数量减少,骨小梁分离增加,骨髓矿化增强,破骨活性增加,循环GH-IGF1-IGFBP3水平降低。然而,局部胫骨近端RT-PCR反应结果显示IGF1上调,IGFBP3下调。结论短时间内摄入高剂量ATRA可降低发育动物GH-IGF1-IGFBP3水平,影响软骨和骨骼稳态,抑制骨骼生长。
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来源期刊
Growth Hormone & Igf Research
Growth Hormone & Igf Research 医学-内分泌学与代谢
CiteScore
3.30
自引率
0.00%
发文量
38
审稿时长
57 days
期刊介绍: Growth Hormone & IGF Research is a forum for research on the regulation of growth and metabolism in humans, animals, tissues and cells. It publishes articles on all aspects of growth-promoting and growth-inhibiting hormones and factors, with particular emphasis on insulin-like growth factors (IGFs) and growth hormone. This reflects the increasing importance of growth hormone and IGFs in clinical medicine and in the treatment of diseases.
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