Research findings working with the p53 and Rb1 targeted osteosarcoma mouse model.
Research findings working with the p53 and Rb1 targeted osteosarcoma mouse model.
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DOI：
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发表时间：
2014-05
影响因子：
5.3
通讯作者：
Yaojuan Lu;S. Gitelis;G. Lei;M. Ding;C. Maki;Ranim R. Mira;Qiping Zheng
中科院分区：
文献类型：
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作者：
Yaojuan Lu;S. Gitelis;G. Lei;M. Ding;C. Maki;Ranim R. Mira;Qiping Zheng
骨肉瘤（OS）是儿童和年轻人最常见的骨癌。骨肉瘤的病因目前尚不清楚。除了主要的成骨细胞外，肿瘤组织中存在形成软骨的软骨细胞，提示软骨形成在骨肉瘤发展中的作用。Runx 2是成骨细胞分化和软骨细胞成熟的主要转录因子。有趣的是，RUNX 2已被证明与p53和Rb 1直接相互作用，这两个基因对小鼠骨肉瘤的发展至关重要。然而，Runx 2在骨肉瘤进展过程中的体内相关性尚未阐明。我们最近发现，靶向肥大软骨细胞中的Runx 2表达延迟了软骨细胞的成熟。也有研究表明，成骨细胞特异性缺失p53和Rb 1基因在小鼠中形成骨肉瘤。在这里，我们报告我们最近的研究结果，使用这些骨肉瘤小鼠模型以及人类骨肉瘤组织。我们在人成骨细胞型骨肉瘤中检测到高水平的RUNX 2表达，而成软骨细胞型骨肉瘤以软骨样基质为主。为了最小化品系差异的影响，我们将osterix-Cre小鼠回交到同源FVB/N遗传背景上。我们还检测到低GC含量（36%）的floxed Rb 1基因的序列，并证明，加入BSA到反应体系中增加了floxed Rb 1基因的PCR基因分型的效率。最后，我们成功地建立了多个骨肉瘤小鼠模型，有或没有Runx 2转基因背景。这些小鼠表现出异质性骨肉瘤表型和标志基因表达。这些小鼠的特征将有助于理解Runx 2在骨肉瘤发病机制中的作用，并可能用于骨肉瘤治疗。
Osteosarcoma (OS) is the most common bone cancer in children and young adults. The etiology of osteosarcoma is currently unknown. Besides the predominant osteoblasts, the presence of cartilage forming chondrocytes within its tumor tissues suggests a role of chondrogenesis in osteosarcoma development. Runx2 is a master transcription factor both for osteoblast differentiation and for chondrocyte maturation. Interestingly, RUNX2 has been shown to directly interact with p53 and Rb1, two genes essential for osteosarcoma development in mice. However the in vivo relevance of Runx2 during osteosarcoma progression has not been elucidated. We have recently shown that targeting Runx2 expression in hypertrophic chondrocytes delays chondrocyte maturation. It has also been shown that osteoblast-specific deletion of p53 and Rb1 genes developed osteosarcoma in mice. Here, we report our recent research findings using these osteosarcoma mouse models as well as human osteosarcoma tissues. We have detected high-level RUNX2 expression in human osteoblastic osteosarcoma, while chondroblastic osteosarcoma is predominant with chondroid matrix. To minimize the effect of strain difference, we have backcrossed osterix-Cre mice onto congenic FVB/N genetic background. We also detected low-GC content (36%) in sequence around the floxed Rb1 gene and demonstrated that addition of BSA into the reaction system increases the efficiency of PCR genotyping of floxed Rb1 gene. Finally, we successfully generated multiple osteosarcoma mouse models with or without Runx2 transgenic background. These mice showed heterogeneous osteosarcoma phenotypes and marker gene expression. Characterization of these mice will facilitate understanding the role of Runx2 in osteosarcoma pathogenesis and possibly, for osteosarcoma treatment.