Role of Runx genes in chondrocyte differentiation
Role of Runx genes in chondrocyte differentiation
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DOI：
10.1006/dbio.2002.0640
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发表时间：
2002-05-01
影响因子：
2.7
通讯作者：
Mundlos, S
中科院分区：
文献类型：
--
作者：
Stricker, S;Fundele, R;Mundlos, S
Runx 2/Cbfa 1在骨骼发育中起核心作用，如具有失活Runx 2/Cbfa 1等位基因的小鼠中成骨细胞/骨的缺乏所证明的。为了进一步研究Runx 2在软骨分化中的作用，并评估Runx 2诱导骨形成的潜力，我们克隆了鸡Runx 2，并使用逆转录病毒系统在鸡胚中过表达。感染鸡翅膀表现出多种表型，包括（1）关节融合，（2）腕部元件的扩张，和（3）骨骼元件的缩短。相反，骨形成不受影响。为了研究Runx 2/Cbfa 1在软骨发育过程中的功能，我们已经产生了在软骨中表达Runx 2显性阴性形式的转基因小鼠。软骨细胞中Runx 2的选择性失活导致肢体严重缩短，这是由于软骨细胞分化、血管侵袭、破骨细胞分化和骨膜骨形成的干扰。对转基因小鼠和鸡肢中生长板的分析表明，Runx 2是软骨细胞分化和血管侵袭的正调节因子。结果进一步表明Runx 2通过维持或通过启动早期软骨细胞分化来促进软骨形成。此外，Runx 2是必需的，但不足以诱导成骨细胞分化。为了分析Runx基因在骨骼发育中的作用，我们用Runx 2和Runx 3特异性探针进行了原位杂交。这两个基因在软骨凝聚中共表达，表明在早期软骨细胞分化的调节中起协同作用，从而解释了感染鸡肢的腕关节和关节中软骨的扩张/维持。(C)2002 Elsevier Science（美国）。
Runx2/Cbfa1 plays a central role in skeletal development as demonstrated by the absence of osteoblasts/bone in mice with inactivated Runx2/Cbfa1 alleles. To further investigate the role of Runx2 in cartilage differentiation and to assess the potential of Runx2 to induce bone formation, we cloned chicken Runx2 and overexpressed it in chick embryos using a retroviral system. Infected chick wings showed multiple phenotypes consisting of (1) joint fusions, (2) expansion of carpal elements, and (3) shortening of skeletal elements. In contrast, bone formation was not affected. To investigate the function of Runx2/Cbfa1 during cartilage development, we have generated transgenic mice that express a dominant negative form of Runx2 in cartilage. The selective inactivation of Runx2 in chondrocytes results in a severe shortening of the limbs due to a disturbance in chondrocyte differentiation, vascular invasion, osteoclast differentiation, and periosteal bone formation. Analysis of the growth plates in transgenic mice and in chick limbs shows that Runx2 is a positive regulator of chondrocyte differentiation and vascular invasion. The results further indicate that Runx2 promotes chondrogenesis either by maintaining or by initiating early chondrocyte differentiation. Furthermore, Runx2 is essential but not sufficient to induce osteoblast differentiation. To analyze the role of runx genes in skeletal development, we performed in situ hybridization with Runx2- and Runx3-specific probes. Both genes were coexpressed in cartilaginous condensations, indicating a cooperative role in the regulation of early chondrocyte differentiation and thus explaining the expansion/maintenance of cartilage in the carpus and joints of infected chick limbs. (C) 2002 Elsevier Science (USA).