Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction.
Open accessAbstract
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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Conditional ablation of osteocytes in mice causes rapid bone loss with increased bone resorption, increased skeletal RANKL mRNA, and an increased RANKL:OPG ratio.
“The conditional ablation of osteoctyes in mice was associated with rapid bone loss in association with increased bone resorption, increased skeletal expression of RANKL mRNA, and an increased RANKL:OPG ratio (123).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [123]
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Uda, Y., Saini, V., Petty, C. A., Alshehri, M., Shi, C., Spatz, J. M., Santos, R., Newell, C. M., Huang, T. Y., Kochen, A., et al. (2021) · Aging · doi:10.18632/aging.203808 · Cited by 20 · see citing works
Hongo, H., Hasegawa, T., Saito, M., Tsuboi, K., Yamamoto, T., Sasaki, M., Abe, M., Henrique Luiz de Freitas, P., Yurimoto, H., Udagawa, N., et al. (2020) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155420961375 · Cited by 12 · see citing works
Self-citation
- 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
- bronze
- doi.org
- Licence
- 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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