Cyp26b1 within the growth plate regulates bone growth in juvenile mice
Cyp26b1 within the growth plate regulates bone growth in juvenile mice
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DOI：
10.1016/j.bbrc.2014.10.001
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发表时间：
2014-11-07
影响因子：
3.1
通讯作者：
Tsumaki, Noriyuki
中科院分区：
文献类型：
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作者：
Minegishi, Yoshiki;Sakai, Yasuo;Tsumaki, Noriyuki
视黄酸（RA）是维生素A的活性代谢产物，在胚胎发育过程中起重要作用。CYP26酶降解RA并具有产生RA梯度的特定表达模式，其调节胚胎中各种结构的模式。然而，尚未解决RA梯度是否也存在并在出生后的器官中发挥作用。我们发现，生长板软骨骨干部分的局部RA活动与Cyp26b1在幼年小鼠骨骺部分的特异性表达有关。为了干扰RA的分布，我们产生了在软骨细胞中特异性缺乏Cyp26b1的小鼠（Cyp26b1（Delta chon）cKO）。这些小鼠在幼年阶段显示骨骼生长减少。此外，它们的生长板软骨显示增殖软骨细胞的增殖率降低，这与增殖软骨细胞区的高度降低有关，并且在4周龄时局部闭合，而野生型小鼠生长板从未闭合。给Cyp26b1 cKO小鼠喂食维生素A缺乏的饮食部分逆转了生长板软骨的这些异常。这些结果共同表明，Cyp26b1在生长板调节软骨细胞的增殖率，并负责生长板的正常功能和生长的骨骼在幼年小鼠，可能是通过限制RA分布在生长板增殖区。(C)2014爱思唯尔公司All rights reserved.
Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1(Delta chon) cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone. (C) 2014 Elsevier Inc. All rights reserved.