SP7 inhibits osteoblast differentiation at a late stage in mice
| Autor: | Hisato Komori, Satoru Toyosawa, Takeshi Moriishi, Masako Mori, Ryo Fukuyama, Tatsuya Furuichi, Toshihisa Komori, Kenji Takada, Carolina A. Yoshida, Keishi Kawasaki, Hiroshi Kawaguchi, Kouhei Nakamura, Wenguang Liu, Toshihiro Miyazaki, Zenjiro Maruyama, Kei Yamana |
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| Rok vydání: | 2011 |
| Předmět: |
Anatomy and Physiology
Cellular differentiation lcsh:Medicine Gene Expression Core Binding Factor Alpha 1 Subunit Mice Genes Reporter Molecular Cell Biology lcsh:Science Promoter Regions Genetic Musculoskeletal System Regulation of gene expression Multidisciplinary musculoskeletal neural and ocular physiology Osteoblast Cell Differentiation Up-Regulation Extracellular Matrix RUNX2 medicine.anatomical_structure Sp7 Transcription Factor Medicine Genetic Engineering Research Article Biotechnology Genetically modified mouse musculoskeletal diseases Chromatin Immunoprecipitation Transgene Mice Transgenic Biology Real-Time Polymerase Chain Reaction Models Biological Osteocytes Bone and Bones Molecular Genetics medicine Genetics Animals Transcription factor Osteoblasts lcsh:R Computational Biology Molecular biology Gene Expression Regulation lcsh:Q Transcription Factors Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 3, p e32364 (2012) |
| ISSN: | 1932-6203 |
| Popis: | 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. PLoS ONE, 7(3), e32364; 2012 |
| Databáze: | OpenAIRE |
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