Osteocyte Apoptosis Controls Activation of Intracortical Resorption in Response to Bone Fatigue
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Osteocyte apoptosis is spatially and temporally linked to bone fatigue-induced microdamage and to subsequent intracortical remodeling. Specifically, osteocytes surrounding fatigue microcracks in bone undergo apoptosis, and those regions containing apoptotic osteocytes co-localize exactly with areas subsequently resorbed by osteoclasts. Here we tested the hypothesis that osteocyte apoptosis is a key controlling step in the activation and/or targeting of osteoclastic resorption after bone fatigue. We carried out in vivo fatigue loading of ulna from 4- to 5-mo-old Sprague-Dawley rats treated with an apoptosis inhibitor (the pan-caspase inhibitor Q-VD-OPh) or with vehicle. Intracortical bone remodeling and osteocyte apoptosis were quantitatively assessed by standard histomorphometric techniques on day 14 after fatigue. Continuous exposure to Q-VD-OPh completely blocked both fatigue-induced apoptosis and the activation of osteoclastic resorption, whereas short-term caspase inhibition during only the first 2 days after fatigue resulted in >50% reductions in both osteocyte apoptosis and bone resorption. These results (1) show that osteocyte apoptosis is necessary to initiate intracortical bone remodeling in response to fatigue microdamage, (2) indicate a possible dose-response relationship between the two processes, and (3) suggest that early apoptotic events after fatigue-induced microdamage may play a substantial role in determining the subsequent course of tissue remodeling.
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Osteocyte apoptosis acts as a chemotactic signal for local osteoclast recruitment.
“Osteocyte apoptosis has been shown to act as a chemotactic signal for local osteoclast recruitment [70, 150, 152, 190, 191].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [191]
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- Authors
- Cardoso, L., Herman, B. C., Verborgt, O., Laudier, D., Majeska, R. J., & Schaffler, M. B.
- Affiliations
- These authors contributed equally to this study
- Icahn School of Medicine at Mount Sinai (US)
- AZ Sint-Lucas (BE)
- City College of New York (US)
- Corresponding author
- Schaffler, Mitchell B
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-04-01
- Volume
- 24
- Issue
- 4
- Pages
- 597-605
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- PMC
- PMC2659511
- OpenAlex
- W2021115829
- Cited by
- 340
- References
- 88
- Citations by year
- 2026: 11 · 2025: 6 · 2024: 11 · 2023: 8 · 2022: 13 · 2021: 23 · 2020: 22 · 2019: 15 · 2018: 18 · 2017: 18 · 2016: 24 · 2015: 26 · 2014: 27 · 2013: 26 · 2012: 28
- FWCI
- 8.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Aeronautics and Space Administration (NASA NCC 9‐58, NCC958)
- National Space Biomedical Research Institute (NASA NCC 9‐58, NCC 9‐58)
- National Institutes of Health (NCC9-58)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR41210, R01AR041210)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- osteocyte apoptosis, bone fatigue, osteoclast resorption, bone microdamage, caspase inhibition, Q-VD-OPh, ulna
- MeSH terms
- Amino Acid Chloromethyl Ketones, Animals, Bone and Bones, Bone Resorption, Cell Differentiation, Cells, Cultured, Enzyme Inhibitors, Female, Osteoclasts, Osteocytes, Quinolines, Time Factors, Weight-Bearing, Bone Remodeling, Rats, Sprague-Dawley, Apoptosis, Rats, Caspase Inhibitors
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