大剂量全反式维甲酸对幼年大鼠纵向骨生长的影响。

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

机构信息

Department of Orthopedic of Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China; Stem Cell Biology and Therapy Laboratory, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.

出版信息

Growth Horm IGF Res. 2022 Feb;62:101446. doi: 10.1016/j.ghir.2022.101446. Epub 2022 Feb 5.

DOI:10.1016/j.ghir.2022.101446

PMID:35149382

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.

摘要

目的

由 GH-IGF1-IGFBP3 组成的信号轴是青春期前影响身高发育的主要信号。据报道，接受维甲酸化疗治疗的肿瘤患儿会出现生长板变薄甚至过早闭合，导致长骨发育不良。尽管接受了 GH 治疗，但仍可能出现生长发育迟缓，但原因尚不清楚。本研究旨在探讨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

将 20 只 3 周龄雄性 SD 大鼠随机分为对照组和实验组（n=10）。大鼠分别给予或不给予大剂量 ATRA 灌胃 10 天。每日记录大鼠体重。实验结束时，测量鼻尾和胫骨长度，对胫骨和肝脏进行病理组织和 RT-PCR 反应染色，并测量血清 GH、IGF1 和 IGFBP3 等水平。

结果

与对照组相比，实验组大鼠体重减轻，鼻尾和胫骨长度缩短。肝脏中 Cyp26b1 酶活性升高，组织病理学染色显示软骨骺板变窄，骨小梁骨髓腔稀疏，骨小梁数量减少，骨小梁分离增加，骨髓矿化增强，破骨细胞活性增强，循环 GH-IGF1-IGFBP3 水平降低。然而，局部近侧胫骨的 RT-PCR 反应结果显示 IGF1 上调，IGFBP3 下调。