Targeted Disruption of Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts
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A transcription factor, Cbfa1, which belongs to the runt-domain gene family, is expressed restrictively in fetal development. To elucidate the function of Cbfa1, we generated mice with a mutated Cbfa1 locus. Mice with a homozygous mutation in Cbfa1 died just after birth without breathing. Examination of their skeletal systems showed a complete lack of ossification. Although immature osteoblasts, which expressed alkaline phophatase weakly but not Osteopontin and Osteocalcin, and a few immature osteoclasts appeared at the perichondrial region, neither vascular nor mesenchymal cell invasion was observed in the cartilage. Therefore, our data suggest that both intramembranous and endochondral ossification were completely blocked, owing to the maturational arrest of osteoblasts in the mutant mice, and demonstrate that Cbfa1 plays an essential role in osteogenesis.
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Runx2 is a master gene of osteoblast differentiation, as demonstrated by Runx2-null mice being devoid of osteoblasts.
“Additionally, Runx2 is a master gene of osteoblast differentiation, as demonstrated by the fact that Runx2-null mice are devoid of osteoblasts [26, 27].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [27]
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- Authors
- Komori, T., Yagi, H., Nomura, S., Yamaguchi, A., Sasaki, K., Deguchi, K., Shimizu, Y., Bronson, R. T., Gao, Y.-H., Inada, M., Sato, M., Okamoto, R., Kitamura, Y., Yoshiki, S., & Kishimoto, T.
- Affiliations
- Osaka University Hospital (JP)
- The University of Osaka (JP)
- SHOWA Medical University (JP)
- Tufts University (US)
- Osaka City University (JP)
- Corresponding author
- Yoshiki, S
- Kishimoto, T
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1997-05
- Volume
- 89
- Issue
- 5
- Pages
- 755-764
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1997812904
- Cited by
- 4,244
- References
- 68
- Citations by year
- 2026: 52 · 2025: 63 · 2024: 76 · 2023: 104 · 2022: 104 · 2021: 152 · 2020: 143 · 2019: 132 · 2018: 127 · 2017: 196 · 2016: 156 · 2015: 186 · 2014: 214 · 2013: 184 · 2012: 177
- FWCI
- 28.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Runx2, osteoblast maturation, bone formation, intramembranous ossification, endochondral ossification, osteoblasts, osteoclasts, perichondrium, skeletal development, mouse mutants, alkaline phosphatase, osteocalcin, osteopontin
- MeSH terms
- Animals, Bone Development, Cell Differentiation, Mice, Mutant Strains, Mutation, Neoplasm Proteins, Osteoblasts, Transcription Factors, Gene Expression Regulation, Developmental, Core Binding Factor Alpha 1 Subunit, Mice
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