Smad1 在骨骼发育和出生后骨形成中发挥着重要作用。
Smad1 plays an essential role in bone development and postnatal bone formation.
机构信息
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA.
出版信息
Osteoarthritis Cartilage. 2011 Jun;19(6):751-62. doi: 10.1016/j.joca.2011.03.004. Epub 2011 Mar 21.
OBJECTIVES
To determine the role of Smad1 in bone development and postnatal bone formation.
METHODS
Col2a1-Cre transgenic mice were bred with Smad1(fx/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. Smad1(fx/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.
RESULTS
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.
CONCLUSIONS
Smad1 plays an essential role in bone development and postnatal bone formation.
目的
确定 Smad1 在骨骼发育和出生后骨形成中的作用。
方法
将 Col2a1-Cre 转基因小鼠与 Smad1(fx/fx) 小鼠杂交，产生软骨细胞特异性 Smad1 条件性敲除 (cKO) 小鼠。进行胚胎骨骼准备和染色，检查分离的原代细胞中的碱性磷酸酶活性 (ALP) 和相对基因表达。还将 Smad1(fx/fx) 小鼠与 Col1a1-Cre 转基因小鼠杂交，产生成骨细胞特异性 Smad1 cKO 小鼠。通过微计算机断层扫描 (μCT) 和 2 月龄小鼠的组织学分析评估出生后骨形成。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。
结果
具有软骨细胞和成骨细胞特异性 Smad1 基因缺失的小鼠具有活力和生育能力。软骨细胞特异性 Smad1 cKO 小鼠的颅骨骨发育延迟。在成骨细胞特异性 Smad1 cKO 小鼠中，BMP 信号部分被抑制，小鼠表现出骨质疏松表型。成骨细胞特异性 Smad1 cKO 小鼠中的成骨细胞增殖和分化受损。
结论
Smad1 在骨骼发育和出生后骨形成中发挥重要作用。
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