Ectopic expression of SOX9 in osteoblasts alters bone mechanical properties.
Ectopic expression of SOX9 in osteoblasts alters bone mechanical properties.
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DOI：
10.1007/s00223-011-9550-9
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发表时间：
2012-02
影响因子：
4.2
通讯作者：
Zhou, Guang
中科院分区：
文献类型：
--
作者：
Liang, Bojian;Cotter, Meghan M.;Chen, Dongxing;Hernandez, Christopher J.;Zhou, Guang
骨质疏松症是一种常见的骨骼疾病，其特征在于低骨量和骨组织的微结构退化，从而增加骨脆性和骨折易感性。我们以前证明，Col 1a 1-SOX 9转基因小鼠，其中SOX 9特异性表达的成骨细胞驱动的2.3kb的Col 1a 1启动子，显示骨质疏松症在出生后早期阶段。在这项研究中，为了进一步分析骨量减少表型，特别是成骨细胞特异性表达的SOX 9对骨力学性能的影响，我们进行了骨几何形状和力学性能分析的长骨从Col 1a 1-SOX 9转基因小鼠（TG）和野生型同窝小鼠（WT）在不同的时间点。有趣的是，在体重调整后，TG小鼠具有与WT小鼠相似的全骨强度，但表现出显著更薄的皮质骨，更低的弹性模量和更高的转动惯量。因此，成骨细胞特异性S 0X 9表达导致骨结构和材料性质改变。此外，与WT小鼠相比，TG小鼠中的Pcna、Col 1a 1、骨钙素和Opg/Rankl比率的表达水平在4月龄之前显著较低，表明TG小鼠具有失调的骨稳态。最后，从TG小鼠中分离的骨髓基质细胞（MSC）在体外显示增强的脂肪细胞分化和成骨细胞分化减少，表明成骨细胞特异性表达SOX 9可导致间充质干细胞分化潜能改变。总之，我们的研究表明，SOX 9活性必须在成人骨骼中受到严格调控，以确保最佳的骨质量。
Osteoporosis is a common skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. We previously demonstrated that Col1a1-SOX9 transgenic mice, in which SOX9 specifically expresses in osteoblasts driven by a 2.3kb Col1a1 promoter, display osteopenia during the early postnatal stage. In this study, to further analyze the osteopenia phenotype and especially the effect of the osteoblast-specific expression of SOX9 on bone mechanical properties, we performed bone geometry and mechanical property analysis of long bones from Col1a1-SOX9 transgenic mice (TG) and wild type littermates (WT) at different time points. Interestingly, after body weight adjustment, TG mice have similar whole-bone strength as WT mice, but exhibit significantly thinner cortical bone, lower elastic modulus, and higher moment of inertia. Thus, osteoblast-specific SOX9 expression results in altered bone structure and material properties. Furthermore, the expression levels of Pcna, Col1a1, Osteocalcin, and the Opg/Rankl ratio in TG mice are significantly lower until 4 months of age compared with WT mice, suggesting that TG mice have dysregulated bone homeostasis. Finally, bone marrow stromal cells (MSCs) isolated from TG mice display enhanced adipocyte differentiation and decreased osteoblast differentiation in vitro, suggesting that osteoblast-specific expression of SOX9 can lead to altered mesenchymal stem cell differentiation potentials. In conclusion, our study implies that SOX9 activity has to be tightly regulated in adult skeleton to ensure optimal bone quality.
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影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
5.3
作者：
Lefebvre, V;Huang, WD;deCrombrugghe, B
通讯作者：
deCrombrugghe, B
DOI：
10.1073/pnas.0504750102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Akiyama, H;Kim, JE;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
5.3
作者：
Geoffroy, V;Kneissel, M;Matthias, P
通讯作者：
Matthias, P
Osf2/Cbfa1：成骨细胞分化的转录激活因子
影响因子：
64.5
作者：
Ducy, P;Zhang, R;Karsenty, G
通讯作者：
Karsenty, G