Glucocorticoid suppression of osteocyte perilacunar remodeling is associated with subchondral bone degeneration in osteonecrosis
Abstract
Through a process called perilacunar remodeling, bone-embedded osteocytes dynamically resorb and replace the surrounding perilacunar bone matrix to maintain mineral homeostasis. The vital canalicular networks required for osteocyte nourishment and communication, as well as the exquisitely organized bone extracellular matrix, also depend upon perilacunar remodeling. Nonetheless, many questions remain about the regulation of perilacunar remodeling and its role in skeletal disease. We find that suppression of osteocyte-driven perilacunar remodeling, a fundamental cellular mechanism, plays a critical role in the glucocorticoid-induced osteonecrosis. In glucocorticoid-treated mice, we find that glucocorticoids coordinately suppress expression of several proteases required for perilacunar remodeling while causing degeneration of the osteocyte lacunocanalicular network, collagen disorganization, and matrix hypermineralization; all of which are apparent in human osteonecrotic lesions. Therefore, osteocyte-mediated perilacunar remodeling maintains bone homeostasis, is dysregulated in skeletal disease, and may represent an attractive therapeutic target for the treatment of osteonecrosis.
- Authors:
-
- Univ. of California, San Francisco, CA (United States). Dept. of Orthopaedic Surgery
- Univ. of California, San Francisco, CA (United States). Dept. of Orthopaedic Surgery; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Univ. of California, San Francisco, CA (United States). Dept. of Orthopaedic Surgery; Univ. of California, Berkeley, CA (United States)
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States). Dept. of Materials Science and Engineering
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1411656
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 7; Journal ID: ISSN 2045-2322
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Fowler, Tristan W., Acevedo, Claire, Mazur, Courtney M., Hall-Glenn, Faith, Fields, Aaron J., Bale, Hrishikesh A., Ritchie, Robert O., Lotz, Jeffrey C., Vail, Thomas P., and Alliston, Tamara. Glucocorticoid suppression of osteocyte perilacunar remodeling is associated with subchondral bone degeneration in osteonecrosis. United States: N. p., 2017.
Web. doi:10.1038/srep44618.
Fowler, Tristan W., Acevedo, Claire, Mazur, Courtney M., Hall-Glenn, Faith, Fields, Aaron J., Bale, Hrishikesh A., Ritchie, Robert O., Lotz, Jeffrey C., Vail, Thomas P., & Alliston, Tamara. Glucocorticoid suppression of osteocyte perilacunar remodeling is associated with subchondral bone degeneration in osteonecrosis. United States. https://doi.org/10.1038/srep44618
Fowler, Tristan W., Acevedo, Claire, Mazur, Courtney M., Hall-Glenn, Faith, Fields, Aaron J., Bale, Hrishikesh A., Ritchie, Robert O., Lotz, Jeffrey C., Vail, Thomas P., and Alliston, Tamara. Wed .
"Glucocorticoid suppression of osteocyte perilacunar remodeling is associated with subchondral bone degeneration in osteonecrosis". United States. https://doi.org/10.1038/srep44618. https://www.osti.gov/servlets/purl/1411656.
@article{osti_1411656,
title = {Glucocorticoid suppression of osteocyte perilacunar remodeling is associated with subchondral bone degeneration in osteonecrosis},
author = {Fowler, Tristan W. and Acevedo, Claire and Mazur, Courtney M. and Hall-Glenn, Faith and Fields, Aaron J. and Bale, Hrishikesh A. and Ritchie, Robert O. and Lotz, Jeffrey C. and Vail, Thomas P. and Alliston, Tamara},
abstractNote = {Through a process called perilacunar remodeling, bone-embedded osteocytes dynamically resorb and replace the surrounding perilacunar bone matrix to maintain mineral homeostasis. The vital canalicular networks required for osteocyte nourishment and communication, as well as the exquisitely organized bone extracellular matrix, also depend upon perilacunar remodeling. Nonetheless, many questions remain about the regulation of perilacunar remodeling and its role in skeletal disease. We find that suppression of osteocyte-driven perilacunar remodeling, a fundamental cellular mechanism, plays a critical role in the glucocorticoid-induced osteonecrosis. In glucocorticoid-treated mice, we find that glucocorticoids coordinately suppress expression of several proteases required for perilacunar remodeling while causing degeneration of the osteocyte lacunocanalicular network, collagen disorganization, and matrix hypermineralization; all of which are apparent in human osteonecrotic lesions. Therefore, osteocyte-mediated perilacunar remodeling maintains bone homeostasis, is dysregulated in skeletal disease, and may represent an attractive therapeutic target for the treatment of osteonecrosis.},
doi = {10.1038/srep44618},
journal = {Scientific Reports},
number = ,
volume = 7,
place = {United States},
year = {Wed Mar 22 00:00:00 EDT 2017},
month = {Wed Mar 22 00:00:00 EDT 2017}
}
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