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Cited by 141Bone Metabolism and DiseasesCell Adhesion Molecules ResearchBone and Dental Protein Studies

Impaired Bone Formation in Transgenic Mice Resulting from Altered Integrin Function in Osteoblasts

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Zimmerman, Deborah, Jin, Fang, Leboy, Phoebe, Hardy, Stephen, Damsky, Caroline·2000·Developmental Biology
DOI 10.1006/dbio.2000.9633
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Abstract

To determine the role of integrins in mature osteoblasts in vivo, we expressed in transgenic mice a dominant-negative integrin subunit (beta1-DN) consisting of the beta1 subunit cytoplasmic and transmembrane domains, driven by the osteoblast-specific osteocalcin promoter. Immature osteoblasts isolated from transgenic animals differentiated normally in vitro until the osteocalcin promoter became active; thereafter they detached from the substratum, suggesting that beta1-DN was impairing adhesion in mature osteoblasts. Transgenic animals had reduced bone mass, with increased cortical porosity in long bones and thinner flat bones in the skull. At 35 days, the rate of bone formation was reduced in cortical bone, and the parietal bones were 45% thinner than in wild-type animals. Active osteoblasts were less polar and had larger areas of cytoplasm with intracellular stores of matrix molecules. Osteocyte lacunae appeared normal around the cell body but did not have normal canilicular structures. At 90 days, the parietal bone of transgenic males was of normal width, suggesting that the original defect in matrix deposition had been repaired or compensated for. In contrast, transgenic females still had decreased bone mass in the parietal bone at 90 days. The decreased bone mass in TG females was accompanied by increased staining for osteoclast activity, suggesting that there was a sex-specific defect in mature animals.

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Authors
Zimmerman, D., Jin, F., Leboy, P., Hardy, S., & Damsky, C.
Affiliations
  • University of California, San Francisco (US)
  • University of Pennsylvania (US)
ORCID
Jin, Fang
Venue
Developmental Biology
Publisher
Elsevier BV
Published
2000-04
Volume
220
Issue
1
Pages
2-15
ISSN
0012-1606 (ISSN-L)
DOI
10.1006/dbio.2000.9633
OpenAlex
W2034014800
Cited by
141
References
39
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 8 · 2018: 7 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 12 · 2013: 6 · 2012: 2
FWCI
3.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Arthritis Foundation
  • University of California, San Francisco
  • National Institute of Dental and Craniofacial Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
Keywords
beta1 integrin, osteoblasts, bone formation, osteocalcin promoter, transgenic mice, cell adhesion, bone mass, cortical porosity, osteocyte lacunae, sex differences, osteoclast activity, extracellular matrix deposition
MeSH terms
Animals, Bone and Bones, Bone Development, Bone Resorption, Cell Adhesion, Extracellular Matrix, Female, Male, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Models, Biological, Osteoblasts, Osteoclasts, Promoter Regions, Genetic, Signal Transduction, Osteocalcin, Gene Expression Regulation, Developmental, Integrin beta1, Mice, In Vitro Techniques

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