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Osteocyte Apoptosis Controls Activation of Intracortical Resorption in Response to Bone Fatigue
Open accessAbstract
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 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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Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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