Absence of transcription factor c-maf causes abnormal terminal differentiation of hypertrophic chondrocytes during endochondral bone development
Absence of transcription factor c-maf causes abnormal terminal differentiation of hypertrophic chondrocytes during endochondral bone development
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DOI：
10.1016/s0012-1606(03)00324-5
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发表时间：
2003-10-01
影响因子：
2.7
通讯作者：
Glimcher, LH
中科院分区：
文献类型：
--
作者：
MacLean, HE;Kim, JI;Glimcher, LH
在这项研究中，我们报道了转录因子c-Maf在软骨内骨发育过程中是正常软骨细胞分化所必需的。C-maf在胎儿发育过程中(E14.5-E18.5)在肥大的软骨细胞中表达，在胫骨中的表达高峰在E15.5和E16.5，在终末分化的软骨细胞中表达最高。在c-maf缺失的小鼠中，胎儿骨骼长度减少了约10%，肥大的软骨细胞分化受到干扰。在c-maf缺失的胫骨中，成熟的肥大软骨细胞数量在E15.5时开始减少，X型胶原和骨桥蛋白的表达域分别减少，分别是肥大软骨细胞和晚期肥大软骨细胞的标志。到E16.5，c-maf(-/-)中有一个晚期肥大的、骨桥蛋白阳性的软骨细胞的扩张域。这种肥大的软骨细胞积聚持续存在，并在4周龄时仍可观察到。提示c-Maf促进软骨细胞的终末分化，并影响肥大软骨细胞的消失。BrdU和TUNEL检测显示c-maf-ull细胞增殖率正常，细胞发生凋亡。在c-maf缺失的EL 5.5处，基质金属蛋白酶-13的表达明显减少。已知基质金属蛋白酶-13受AP-1的调节，也可能是c-Maf的靶点。因此，软骨是一个新的系统，c-Maf在发育过程中发挥作用，而c-Maf是正常软骨细胞分化所必需的。(C)2003 Elsevier Inc.保留所有权利。
In this study, we report that the transcription factor c-Maf is required for normal chondrocyte differentiation during endochondral bone development. c-maf is expressed in hypertrophic chondrocytes during fetal development (E14.5-E18.5), with maximal expression in the tibia occurring at E15.5 and E16.5, in terminally differentiated chondrocytes. In c-maf-null mice, fetal bone length is decreased similar to 10%, and hypertrophic chondrocyte differentiation is perturbed. There is an initial decrease in the number of mature hypertrophic chondrocytes at E15.5 in c-maf-null tibiae, with decreased expression domains of collagen X and osteopontin, markers of hypertrophic and terminal hypertrophic chondrocytes, respectively. By E16.5, there is an expanded domain of late hypertrophic, osteopontin-positive chondrocytes in the c-maf(-/-). This accumulation of hypertrophic chondrocytes persists and is still observed at 4 weeks of age. These data suggest that c-Maf facilitates the initial chondrocyte terminal differentiation and influences the disappearance of hypertrophic chondrocytes. BrdU and TUNEL analyses show normal proliferation rate and apoptosis in the c-maf-null. There is a specific decrease in MMP-13 expression at El 5.5 in the c-maf-null. MMP-13 is known to be regulated by AP-1 and may also be a target of c-Maf. Thus, cartilage is a novel system in which c-Maf acts during development, where c-Maf is required for normal chondrocyte differentiation. (C) 2003 Elsevier Inc. All rights reserved.