The transcription factors L-sox5 and sox6 are essential for cartilage formation
The transcription factors L-sox5 and sox6 are essential for cartilage formation
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DOI：
10.1016/s1534-5807(01)00003-x
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发表时间：
2001-08-01
影响因子：
11.8
通讯作者：
Lefebvre, V
中科院分区：
文献类型：
--
作者：
Smits, P;Li, P;Lefebvre, V
L-Sox 5和Sox 6是高度相同的Sry相关转录因子，在软骨中共表达。Sox 5和Sox 6单缺失小鼠出生时患有轻度骨骼异常，而Sox 5; Sox 6双缺失胎儿则死于严重的全身性软骨发育不良。在这些双突变体中，成软骨细胞分化不良。它们以低水平或不可检测的水平表达所有必需的软骨细胞外基质成分的基因，并在长时间延迟后启动增殖。因此，所有软骨都缺乏细胞外基质并保持不发育。虽然软骨中心的成软骨细胞最终激活肥大前软骨细胞标记，但骺成软骨细胞异位激活肥大软骨细胞标记。厚的膜内骨领发育，但软骨生长板和软骨内骨的形成被破坏。因此，L-Sox 5和Sox 6是成软骨细胞功能的冗余的、有效的增强剂，从而对于软骨内骨骼形成是必需的。
L-Sox5 and Sox6 are highly identical Sry-related transcription factors coexpressed in cartilage. Whereas Sox5 and Sox6 single null mice are born with mild skeletal abnormalities, Sox5; Sox6 double null fetuses die with a severe, generalized chondrodysplasia. In these double mutants, chondroblasts poorly differentiate. They express the genes for all essential cartilage extracellular matrix components at low or undetectable levels and initiate proliferation after a long delay. All cartilages are thus extracellular matrix deficient and remain rudimentary. While chondroblasts in the center of cartilages ultimately activate prehypertrophic chondrocyte markers, epiphyseal chondroblasts ectopically activate hypertrophic chondrocyte markers. Thick intramembranous bone collars develop, but the formation of cartilage growth plates and endochondral bones is disrupted. L-Sox5 and Sox6 are thus redundant, potent enhancers of chondroblast functions, thereby essential for endochondral skeleton formation.