Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA.
Osteoarthritis Cartilage. 2011 Jun;19(6):751-62. doi: 10.1016/j.joca.2011.03.004. Epub 2011 Mar 21.
To determine the role of Smad1 in bone development and postnatal bone formation.
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.
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.
确定 Smad1 在骨骼发育和出生后骨形成中的作用。
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。
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。
Smad1 在骨骼发育和出生后骨形成中发挥重要作用。
