SP7 inhibits osteoblast differentiation at a late stage in mice.
SP7 inhibits osteoblast differentiation at a late stage in mice.
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DOI：
10.1371/journal.pone.0032364
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Komori T
中科院分区：
文献类型：
--
作者：
Yoshida CA;Komori H;Maruyama Z;Miyazaki T;Kawasaki K;Furuichi T;Fukuyama R;Mori M;Yamana K;Nakamura K;Liu W;Toyosawa S;Moriishi T;Kawaguchi H;Takada K;Komori T
RUNX 2和SP 7是成骨细胞早期分化所必需的转录因子。虽然RUNX 2在晚期阶段抑制成骨细胞分化，但SP 7在成骨细胞分化晚期阶段的功能尚未完全阐明。因此，我们追求SP 7在成骨细胞分化中的功能。RUNX 2在Runx 2 −/−颅骨细胞中诱导Sp 7表达。腺病毒转移sh-Sp 7到原代成骨细胞中降低了Alpl、Col 1a 1和Bglap 2的表达和矿化，而Sp 7在成骨细胞分化的晚期降低了Bglap 2的表达和矿化。在2.3kb Col 1a 1启动子控制下的Sp 7转基因小鼠表现出骨量减少和皮质骨中的编织骨样结构，其薄且矿化程度低，呈剂量依赖性。此外，成骨细胞和骨细胞中的突起数量减少。虽然成骨细胞密度增加，但骨形成减少。成骨细胞中BrdU掺入频率增加，而Col 1a 1、Spp 1、Ibsp和Bglap 2的表达减少。此外，在Sp 7/Runx 2双转基因小鼠中，Sp 7或Runx 2转基因小鼠中的骨质减少恶化，并且Col 1a 1和Bglap 2的表达降低。在Runx 2和Sp 7转基因小鼠中，Sp 7和Runx 2的表达分别没有增加。Sp 7转基因小鼠和Sp 7转导的细胞中内源性Sp 7的表达增加; Sp 7的引入激活和sh-Sp 7抑制Sp 7启动子; ChIP检测显示内源性Sp 7结合在Sp 7启动子的近端区域。这些发现表明，SP 7和RUNX 2抑制成骨细胞分化的后期阶段的方式独立于RUNX 2和SP 7，SP 7正调控自己的启动子。
RUNX2 and SP7 are essential transcription factors for osteoblast differentiation at an early stage. Although RUNX2 inhibits osteoblast differentiation at a late stage, the function of SP7 at the late stage of osteoblast differentiation is not fully elucidated. Thus, we pursued the function of SP7 in osteoblast differentiation. RUNX2 induced Sp7 expression in Runx2 −/− calvarial cells. Adenoviral transfer of sh-Sp7 into primary osteoblasts reduced the expression of Alpl, Col1a1, and Bglap2 and mineralization, whereas that of Sp7 reduced Bglap2 expression and mineralization at a late stage of osteoblast differentiation. Sp7 transgenic mice under the control of 2.3 kb Col1a1 promoter showed osteopenia and woven-bone like structure in the cortical bone, which was thin and less mineralized, in a dose-dependent manner. Further, the number of processes in the osteoblasts and osteocytes was reduced. Although the osteoblast density was increased, the bone formation was reduced. The frequency of BrdU incorporation was increased in the osteoblastic cells, while the expression of Col1a1, Spp1, Ibsp, and Bglap2 was reduced. Further, the osteopenia in Sp7 or Runx2 transgenic mice was worsened in Sp7/Runx2 double transgenic mice and the expression of Col1a1 and Bglap2 was reduced. The expression of Sp7 and Runx2 was not increased in Runx2 and Sp7 transgenic mice, respectively. The expression of endogenous Sp7 was increased in Sp7 transgenic mice and Sp7-transduced cells; the introduction of Sp7 activated and sh-Sp7 inhibited Sp7 promoter; and ChIP assay showed the binding of endogenous SP7 in the proximal region of Sp7 promoter. These findings suggest that SP7 and RUNX2 inhibit osteoblast differentiation at a late stage in a manner independent of RUNX2 and SP7, respectively, and SP7 positively regulates its own promoter.
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影响因子：
4.8
作者：
Celil, AB;Campbell, PG
通讯作者：
Campbell, PG
影响因子：
4.8
作者：
Matsubara, Takuma;Kida, Kumiko;Yoneda, Toshiyuki
通讯作者：
Yoneda, Toshiyuki
影响因子：
2.5
作者：
Maruyama, Zenjiro;Yoshida, Carolina A.;Komori, Toshihisa
通讯作者：
Komori, Toshihisa
影响因子：
5.3
作者：
Geoffroy, V;Kneissel, M;Matthias, P
通讯作者：
Matthias, P
影响因子：
64.5
作者：
Nakashima, K;Zhou, X;de Crombrugghe, B
通讯作者：
de Crombrugghe, B