Cited by 848Bone Metabolism and DiseasesBone health and osteoporosis researchSpaceflight effects on biology

Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction.

Open access
Tatsumi, Sawako, Ishii, Kiyoaki, Amizuka, Norio, Li, Minqi, Kobayashi, Toshihiro, Kohno, Kenji, Ito, Masako, Takeshita, Sunao +1 more·2007·Cell Metabolism

Abstract

Bone remodeling is performed by osteoclasts and osteoblasts at the bone surface. Inside of bone is a network of numerous osteocytes, whose specific function has remained an enigma. Here we describe a transgenic mouse model in which inducible and specific ablation of osteocytes is achieved in vivo through targeted expression of diphtheria toxin (DT) receptor. Following a single injection of DT, approximately 70%-80% of the osteocytes, but apparently no osteoblasts, were killed. Osteocyte-ablated mice exhibited fragile bone with intracortical porosity and microfractures, osteoblastic dysfunction, and trabecular bone loss with microstructural deterioration and adipose tissue proliferation in the marrow space, all of which are hallmarks of the aging skeleton. Strikingly, these "osteocyte-less" mice were resistant to unloading-induced bone loss, providing evidence for the role of osteocytes in mechanotransduction. Thus, osteocytes represent an attractive target for the development of diagnostics and therapeutics for bone diseases, such as osteoporosis.

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Crossref · 10.1016/j.cmet.2007.05.001

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Authors
Tatsumi, S., Ishii, K., Amizuka, N., Li, M., Kobayashi, T., Kohno, K., Ito, M., Takeshita, S., & Ikeda, K.
Affiliations
  • National Center for Geriatrics and Gerontology (JP)
  • Niigata University (JP)
  • Nara Institute of Science and Technology (JP)
  • Nagasaki University Hospital (JP)
Corresponding author
Ikeda, Kyoji
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2007-06
Volume
5
Issue
6
Pages
464-475
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2074494444
Cited by
848
References
49
Citations by year
2026: 28 · 2025: 24 · 2024: 26 · 2023: 23 · 2022: 32 · 2021: 45 · 2020: 56 · 2019: 48 · 2018: 35 · 2017: 42 · 2016: 43 · 2015: 69 · 2014: 65 · 2013: 69 · 2012: 62
FWCI
16.41
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology (15390290)
  • National Institute of Biomedical Innovation (06-31, MF-14)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Physiology › Spaceflight effects on biology
Keywords
osteocytes, osteoporosis, mechanotransduction, diphtheria toxin receptor, bone remodeling, osteoblast dysfunction, trabecular bone loss, bone fragility, microfracture, bone unloading, bone aging, marrow adipose tissue, transgenic mouse model
MeSH terms
Adipose Tissue, Animals, Cells, Cultured, Mice, Inbred C57BL, Mice, Transgenic, Osteoblasts, Osteocytes, Osteoporosis, Stress, Mechanical, Intercellular Signaling Peptides and Proteins, Mechanotransduction, Cellular, Cell Proliferation, Mice, Osteoprotegerin, RANK Ligand, Heparin-binding EGF-like Growth Factor

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