Cellular and molecular mechanisms of synovial joint and articular cartilage formation
Cellular and molecular mechanisms of synovial joint and articular cartilage formation
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DOI：
10.1196/annals.1346.010
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Iwamoto, Masahiro
中科院分区：
文献类型：
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作者：
Pacifici, Maurizio;Koyama, Eiki;Iwamoto, Masahiro
滑膜关节和关节软骨在骨骼功能中起着至关重要的作用，但实际上对它们的胚胎发育知之甚少。在这里，我们首先集中在interzone，一个薄的间充质细胞层形成在未来的关节部位，被广泛认为是关节和关节软骨发育的关键。为了确定区间细胞的起源和命运，我们显微注射的重要荧光染料DiI在几个关节周围的网站在鸡四肢和监测的行为和命运的标记细胞随着时间的推移。关节周围的间充质细胞位于紧邻早期关节迁移，成为间带的一部分，并最终被发现在骺关节层和关节囊。在体外分离和培养的Interzone细胞表达典型的表型标志物，包括GDF-5、Wnt-14和CD-44，并随着时间的推移分化为软骨细胞。为了确定关节软骨细胞形成的分子机制，我们对ets转录因子家族成员ERG及其选择性剪接变体C-1-1进行了额外的研究，我们先前发现它们在发育中的禽类关节软骨细胞中表达。我们克隆了禽C-1-1（ERGp 55 Delta 81）的人类对应物，并在软骨特异性Col 2基因启动子-增强子控制下在转基因小鼠中有条件地表达。整个转基因小鼠肢体软骨细胞群体表现出不成熟的关节样表型和生长板形成和软骨细胞成熟的野生型同窝相比，虚拟缺乏。总之，我们的研究表明，关节周围的间充质细胞参与区间和关节层的形成，区间细胞可以分化成软骨细胞，并获得一个永久性的关节软骨细胞表型的援助，并可能决定由ets转录因子ERG。
Synovial joints and articular cartilage play crucial roles in the skeletal function, but relatively little is actually known about their embryonic development. Here we first focused on the interzone, a thin mesenchymal cell layer forming at future joint sites that is widely thought to be critical for joint and articular cartilage development. To determine interzone cell origin and fate, we microinjected the vital fluorescent dye DiI at several peri-joint sites in chick limbs and monitored the behavior and fate of labeled cells over time. Peri-joint mesenchymal cells located immediately adjacent to incipient joints migrated, became part of the interzone, and were eventually found in epiphyseal articular layer and joint capsule. Interzone cells isolated and reared in vitro expressed typical phenotypic markers, including GDF-5, Wnt-14, and CD-44, and differentiated into chondrocytes over time. To determine the molecular Mechanisms of articular chondrocyte formation, we carried out additional studies on the ets transcription factor family member ERG and its alternatively spliced variant C-1-1 that we previously found to be expressed in developing avian articular chondrocytes. We cloned the human counterpart of avian C-1-1 (ERGp55 Delta 81) and conditionally expressed it in transgenic mice under cartilage-specific Col2 gene promotor-enhancer control. The entire transgenic mouse limb chondrocyte population exhibited an immature articular-like phenotype and a virtual lack of growth plate formation and chondrocyte maturation compared to wild-type littermate. Together, our studies reveal that peri-joint mesenchymal cells take part in interzone and articular layer formation, interzone cells can differentiate into chondrocytes, and acquisition of a permanent articular chondrocyte phenotype is aided and perhaps dictated by ets transcription factor ERG.