Cited by 4,244Bone Metabolism and DiseasesAlkaline Phosphatase Research StudiesDevelopmental Biology and Gene Regulation

Targeted Disruption of Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts

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Komori, T, Yagi, H, Nomura, S, Yamaguchi, A, Sasaki, K, Deguchi, K, Shimizu, Y, Bronson, R.T +7 more·1997·Cell

Abstract

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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Crossref · 10.1016/s0092-8674(00)80258-5

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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
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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