Retinoic acid is a potent regulator of growth plate chondrogenesis
Retinoic acid is a potent regulator of growth plate chondrogenesis
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DOI：
10.1210/en.141.1.346
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发表时间：
2000-01-01
期刊：
影响因子：
4.8
通讯作者：
Baron, J
中科院分区：
文献类型：
--
作者：
De Luca, F;Uyeda, JA;Baron, J
维生素 A 缺乏和过量都会导致哺乳动物纵向骨骼生长异常。由于全反式视黄酸 (RA) 是由维生素 A 合成的，因此我们假设 RA 调节生长板软骨形成。与这一假设一致，单次口服剂量的 RA 降低了大鼠近端胫骨生长板的高度。为了确定 RA 是否直接作用于生长板，在 RA 存在的情况下培养胎鼠跖骨。在该系统中，RA通过三种机制抑制纵向骨生长：1）减少软骨细胞增殖（通过H-3-胸苷掺入评估），特别是在生长板的增殖区； 2) 基质合成减少（通过 (SO4)-S-35 掺入糖胺聚糖来评估）； 3) 细胞肥大减少（组织学测定）。 RA 的生长抑制作用可被视黄酸受体 (RAR) 拮抗剂完全逆转。在没有外源性 RA 的情况下，这种拮抗剂会加速骨生长，就像 RA 特异性中和抗体一样，这表明内源性 RA 负向调节生长板软骨形成。我们得出的结论是，RA 通过 RAR 发挥作用，通过抑制生长板软骨细胞增殖、软骨细胞肥大和基质合成来负向调节纵向骨生长。
Vitamin A deficiency and excess both cause abnormalities in mammalian longitudinal bone growth. Because all-trans retinoic acid (RA) is synthesized from vitamin A, we hypothesized that RA regulates growth plate chondrogenesis. Consistent with this hypothesis, a single oral dose of RA reduced the height of the rat proximal tibial growth plate. To determine whether RA acts directly on growth plate, fetal rat metatarsal bones were cultured in the presence of RA. In this system, RA inhibited longitudinal bone growth by three mechanisms: 1) decreased chondrocyte proliferation, (assessed by H-3-thymidine incorporation), particularly in the proliferative zone of the growth plate; 2) decreased matrix synthesis (assessed by (SO4)-S-35 incorporation into glycosaminoglycans); and 3) decreased cell hypertrophy (determined histologically). The growth-inhibiting effects of RA were completely reversed by a retinoic acid receptor (RAR) antagonist. In the absence of exogenous RA, this antagonist accelerated bone growth, as did an RA-specific neutralizing antibody, suggesting that endogenous RA negatively regulates growth plate chondrogenesis. We conclude that RA, acting through RARs, negatively regulates longitudinal bone growth by inhibiting growth plate chondrocyte proliferation, chondrocyte hypertrophy, and matrix synthesis.