Mesenchymal progenitor self-renewal deficiency leads to age-dependent osteoporosis in Sca-1/Ly-6A null mice
Mesenchymal progenitor self-renewal deficiency leads to age-dependent osteoporosis in Sca-1/Ly-6A null mice
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DOI：
10.1073/pnas.1036475100
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发表时间：
2003-05-13
影响因子：
11.1
通讯作者：
Stanford, WL
中科院分区：
文献类型：
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作者：
Bonyadi, M;Waldman, SD;Stanford, WL
年龄依赖性骨质疏松症是西半球最常见的疾病，其细胞和分子机制尚不清楚，部分原因是缺乏适当的动物模型来研究疾病进展。在这里，我们提出了一个模型，显示了许多相似之处，人类疾病。众所周知，Sca-1在造血干细胞上表达，它存在于骨髓基质细胞的一个亚群上，其中可能包括间充质干细胞。纵向研究表明，Sca-1（-/-）小鼠的骨骼发育正常，但随着年龄的增长，骨质急剧下降，导致骨质疏松。在体内和体外分析表明，Sca-1是所需的直接间充质祖细胞的自我更新和破骨细胞分化的调节间接。因此，有缺陷的间充质干细胞或祖细胞的自我更新可能代表了一个以前未表征的机制，年龄依赖性骨质疏松症在人类。
The cellular and molecular mechanisms that underlie age-dependent osteoporosis, the most common disease in the Western Hemisphere, are poorly understood in part due to the lack of appropriate animal models in which to study disease progression. Here, we present a model that shows many similarities to the human disease. Sca-1, well known for its expression on hematopoietic stem cells, is present on a subset of bone marrow stromal cells, which potentially include mesenchymal stem cells. Longitudinal studies showed that Sca-1(-/-)mice undergo normal bone development but with age exhibit dramatically decreased bone mass resulting in brittle bones. In vivo and in vitro analyses demonstrated that Sca-1 is required directly for the self-renewal of mesenchymal progenitors and indirectly for the regulation of osteoclast differentiation. Thus, defective mesenchymal stem or progenitor cell self-renewal may represent a previously uncharacterized mechanism of age-dependent osteoporosis in humans.