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首页> 外文期刊>Molecular and Cellular Biology >Loss of Osteoblast Runx3 Produces Severe Congenital Osteopenia
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Loss of Osteoblast Runx3 Produces Severe Congenital Osteopenia

机译：成骨细胞Runx3的丢失会导致严重的先天性骨质减少

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Congenital osteopenia is a bone demineralization condition that is associated with elevated fracture risk in human infants. Here we show that Runx3, like Runx2, is expressed in precommitted embryonic osteoblasts and that Runx3-deficient mice develop severe congenital osteopenia. Runx3-deficient osteoblast-specific (Runx3fl/fl/Col1α1-cre), but not chondrocyte-specific (Runx3fl/fl/Col1α2-cre), mice are osteopenic. This demonstrates that an osteoblastic cell-autonomous function of Runx3 is required for proper osteogenesis. Bone histomorphometry revealed that decreased osteoblast numbers and reduced mineral deposition capacity in Runx3-deficient mice cause this bone formation deficiency. Neonatal bone and cultured primary osteoblast analyses revealed a Runx3-deficiency-associated decrease in the number of active osteoblasts resulting from diminished proliferation and not from enhanced osteoblast apoptosis. These findings are supported by Runx3-null culture transcriptome analyses showing significant decreases in the levels of osteoblastic markers and increases in the levels of Notch signaling components. Thus, while Runx2 is mandatory for the osteoblastic lineage commitment, Runx3 is nonredundantly required for the proliferation of these precommitted cells, to generate adequate numbers of active osteoblasts. Human RUNX3 resides on chromosome 1p36, a region that is associated with osteoporosis. Therefore, RUNX3 might also be involved in human bone mineralization.
机译：先天性骨质减少是一种与人婴儿骨折风险升高相关的骨骼脱矿质疾病。在这里，我们显示 Runx3 与 Runx2 一样，在预先承诺的胚胎成骨细胞中表达，并且Runx3缺陷小鼠发展为严重的先天性骨质减少。 Runx3缺陷成骨细胞特异性（ Runx3 fl / fl / Col1 α 1 -cre），但不是软骨细胞特定的（ Runx3 fl / fl / Col1 α 2 -cre），小鼠是骨质疏松的。这表明Runx3的成骨细胞自主功能是正常成骨所必需的。骨组织形态计量学表明，Runx3缺陷型小鼠的成骨细胞数量减少和矿物质沉积能力降低，导致了这种骨形成缺陷。新生儿骨骼和培养的原代成骨细胞分析显示，Runx3缺陷相关的活性成骨细胞数量减少是由于增殖减少而不是成骨细胞凋亡增加所致。这些发现得到Runx3无培养物转录组分析的支持，该分析显示成骨细胞标志物水平显着下降，Notch信号成分水平升高。因此，尽管Runx2是成骨细胞谱系承诺所必需的，但Runx3对于这些预先承诺的细胞的增殖是多余的，以生成足够数量的活性成骨细胞。人类 RUNX3 位于1p36号染色体上，该区域与骨质疏松症有关。因此，RUNX3也可能与人体骨骼矿化有关。

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