Cbf beta regulates Runx2 function isoform-dependently in postnatal bone development
| Autor: | Ryo Fukuyama, Takeshi Moriishi, Naoko Kanatani, Takashi Fujita, Wenguang Liu, Satoru Toyosawa, Toshihisa Komori, Toshihiro Miyazaki, Carolina A. Yoshida, Kei Yamana |
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| Rok vydání: | 2006 |
| Předmět: |
Gene isoform
Genetically modified mouse musculoskeletal diseases Transgene osteocyte osteocalcin Core Binding Factor Alpha 1 Subunit Mice Transgenic Core Binding Factor beta Subunit Mice stomatognathic system medicine Animals Protein Isoforms Luciferase Molecular Biology Runx2/Cbfa1 Bone Development biology Cbfβ musculoskeletal neural and ocular physiology Skull Osteoblast Cell Biology musculoskeletal system Growth Inhibitors Cell biology RUNX2 DNA-Binding Proteins medicine.anatomical_structure Animals Newborn Osteocyte embryonic structures osteoblast Cancer research Osteocalcin biology.protein Developmental Biology Protein Binding |
| Zdroj: | Developmental biology. 296(1) |
| ISSN: | 0012-1606 |
| Popis: | Runx2 and Cbfbeta are essential for skeletal development during the embryonic stage. Runx2 has two isoforms with different N-termini. We examined the functions of the Runx2 isoforms and Cbfbeta in postnatal bone development. On luciferase and electrophoretic mobility shift assays, Runx2-I was less active than Runx2-II in the absence of Cbfb, but the two Runx2 isoforms had similar activity levels in the presence of Cbfb. We generated Runx2-I transgenic mice under the control of Col1a1 promoter and Runx2-I/Cbfb and Runx2-II/Cbfb double transgenic mice. Runx2-I transgenic mice showed less severe osteopenia and fragility than Runx2-II transgenic mice due to milder inhibition of both osteoblast maturation and transition to osteocytes, even though the former mice showed higher transgene expression. However, Runx2-I/Cbfb and Runx2-II/Cbfb double transgenic mice had enhanced inhibition of osteoblast maturation, resulting in similar severity of osteopenia and fragility, although the latter mice had less osteocytes. These findings indicate that (1) Runx2-II more strongly inhibits osteoblast maturation and transition to osteocytes than Runx2-I; (2) Cbfbeta regulates Runx2 function isoform-dependently; and (3) Runx2-I activity is highly dependent on Cbfbeta. These findings demonstrate that Runx2 isoforms exert their functions through at least partly different mechanisms and Cbfbeta regulates bone development by regulating Runx2 function isoform-dependently. |
| Databáze: | OpenAIRE |
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