Smad1 plays an essential role in bone development and postnatal bone formation.

Smad1 plays an essential role in bone development and postnatal bone formation.
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DOI:
10.1016/j.joca.2011.03.004
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发表时间:
2011-06
影响因子:
7
通讯作者:
Chen D
Chen D
中科院分区:
医学2区
文献类型:
--
作者:
Wang M;Jin H;Tang D;Huang S;Zuscik MJ;Chen D

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确定Smad1在骨发育和出生后骨形成中的作用。将Col2a1-Cre转基因小鼠与Smad1fx/fx小鼠杂交,产生软骨细胞特异性Smad1条件敲除(cKO)小鼠。进行胚胎骨骼制备和染色,检测分离原代细胞碱性磷酸酶活性(ALP)和相关基因表达。Smad1fx/fx小鼠也与Col1a1-Cre转基因小鼠杂交,产生成骨特异性Smad1 cKO小鼠。采用显微计算机断层扫描(μCT)和组织学分析评价2月龄小鼠出生后骨形成情况。进行矿化骨结节形成测定、5-溴-2′-脱氧尿苷(BrdU)标记和基因表达分析。软骨细胞和成骨细胞特异性缺失Smad1基因的小鼠是可存活和可生育的。软骨细胞特异性Smad1 cKO小鼠颅骨骨发育延迟。在成骨细胞特异性Smad1 cKO小鼠中,BMP信号被部分抑制,小鼠出现骨减少表型。成骨细胞特异性Smad1 cKO小鼠成骨细胞增殖和分化受损。Smad1在骨发育和出生后骨形成中起重要作用。
To determine the role of Smad1 in bone development and postnatal bone formation. Col2a1-Cre transgenic mice were bred with Smad1fx/fx mice to produce chondrocyte-specific Smad1 conditional knockout (cKO) mice. Embryonic skeletal preparation and staining were performed, alkaline phosphatase activity (ALP) and relative gene expression were examined in isolated primary cells. Smad1fx/fx mice were also bred with Col1a1-Cre transgenic mice to produce osteoblast-specific Smad1 cKO mice. Postnatal bone formation was assessed by micro-computed tomography (μCT) and histological analyses in 2-month-old mice. Mineralized bone nodule formation assay, 5-bromo-2′-deoxy-uridine (BrdU) labeling and gene expression analysis were performed. Mice with chondrocyte- and osteoblast-specific deletion of the Smad1 gene are viable and fertile. Calvarial bone development was delayed in chondrocyte-specific Smad1 cKO mice. In osteoblast-specific Smad1 cKO mice, BMP signaling was partially inhibited and mice developed an osteopenic phenotype. Osteoblast proliferation and differentiation were impaired in osteoblast-specific Smad1 cKO mice. Smad1 plays an essential role in bone development and postnatal bone formation.
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