OSTEOPETROSIS IN SRC-DEFICIENT MICE IS DUE TO AN AUTONOMOUS DEFECT OF OSTEOCLASTS
OSTEOPETROSIS IN SRC-DEFICIENT MICE IS DUE TO AN AUTONOMOUS DEFECT OF OSTEOCLASTS
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DOI：
10.1073/pnas.90.10.4485
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发表时间：
1993-05-15
影响因子：
11.1
通讯作者：
SORIANO, P
中科院分区：
文献类型：
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作者：
LOWE, C;YONEDA, T;SORIANO, P
骨硬化症是一种骨塑形障碍，由于破骨细胞（吸收骨的细胞）功能缺陷，导致骨基质过度积聚。携带编码pp60c - src（Src）的基因Src靶向破坏的小鼠会出现这种表型，但尽管该激酶通常存在于多种细胞类型中，却没有表现出其他明显的缺陷。因为Src在成骨细胞和破骨细胞中均有表达，且两者对于正常的骨吸收都是必需的，所以基本缺陷可能发生在这两种细胞类型中的任何一种。在这项研究中，我们使用了体外方法以及将胎肝移植到受辐射的Src缺失受体中，以证明固有缺陷存在于破骨细胞且独立于骨髓微环境。这一结果（i）确定了一种Src功能至关重要且不能被其他相关激酶替代的细胞类型，（ii）应该能够分离出一种对Src特异的底物。
Osteopetrosis is a bone modeling disorder resulting in excessive accumulation of bone matrix due to defective function of osteoclasts, the cells that resorb bone. Mice carrying a targeted disruption of the gene Src that encodes pp60c-src (Src), a nonreceptor protein tyrosine kinase, develop this phenotype but do not exhibit other overt defects despite the fact that the kinase is normally present in a broad variety of cell types. Because Src is expressed in osteoblasts as well as in osteoclasts and both are required for normal bone resorption, the basic defect could occur in either cell type. In this study we have used in vitro approaches and fetal liver transplantation into irradiated Src- recipients to demonstrate that the inherent defect is with osteoclasts and autonomous of the bone marrow microenvironment. This result (i) identifies a cell type in which Src function is essential and cannot be replaced by other related kinases and (ii) should allow the isolation of a substrate that is specific to Src.