Glucocorticoid induced autophagy in osteocytes
Open accessAbstract
Glucocorticoid (GC) therapy is the most frequent cause of secondary osteoporosis. In this study we have demonstrated that GC treatment induced the development of autophagy, preserving osteocyte viability. GC treatment resulted in an increase in autophagy markers and the accumulation of autophagosome vacuoles in vitro and in vivo promoted the onset of the osteocyte autophagy, as determined by expression of autophagy markers in an animal model of GC-induced osteoporosis. An autophagy inhibitor reversed the protective effects of GCs. The effects of GCs on osteocytes were in contrast to tumor necrosis factor α (TNF-α), which induced apoptosis but not autophagy. Together this study reveals a novel mechanism for the effect of GC on osteocytes, shedding new insight into mechanisms responsible for bone loss in patients receiving GC therapy.
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Osteocyte autophagy is crucial to the regulation of bone structure and plays a role in glucocorticoid-induced bone fragility.
“We have reported that osteocyte autophagy is crucial to the regulation of bone structure and plays a role in GC induced bone fragility [44, 68].”
From Prevention of glucocorticoid induced bone changes with beta-ecdysone (2015) · cites this paper as [68]
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“It was recently shown in vitro that osteocyte autophagy increases in response to stresses, such as growth factor starvation, hypoxia, and glucocorticoids [40]; and that increased autophagy plays a protective role against glucocorticoid-induced cell death [41].”
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“(26) In the present study, we report the involvement of autophagy in MM-induced osteocyte deathandrelatedboneremodelingalterations.”
Bone and the Innate Immune System
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Effectors of mTOR-autophagy pathway: targeting cancer, affecting the skeleton
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“Interestingly, glucocorticoids enhance autophagy in osteocytes potently, which has been proposed to explain glucocorticoid-induced osteoporosis [53].”
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“As previously observed [11, 13, 14], treatment of osteocytes with Dex resulted in a dose-dependent increase in autophagasome formation as demonstrated by positive CYTO-ID® staining (Suppl.”
ResultWang, X., Gong, L., Huang, J., Jiang, C., & Yan, Z. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173212 · Cited by 58 · see citing works
Inhaled Corticosteroids and Bone Health
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“demonstrated more than 50% reduction of osteocyte numbers in steroid treated mice [17].”
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“tophagy in osteocytes (14) and/or may increase oxidative”
BackgroundAnimal models to explore the effects of glucocorticoids on skeletal growth and structure.
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“Viable osteocytes are a prerequisite for maintaining bone’s proper material properties and structural integrity, as shown by the observations that apoptosis and/or autophagy of osteocytes leads to decreased bone properties in glucocorticoid excess((4,5)) and triggers bone turnover in fatigue loading.”
BackgroundAutophagy plays an essential role in bone homeostasis
Jaber, F. A., Khan, N. M., Ansari, M. Y., Al-Adlaan, A. A., Hussein, N. J., & Safadi, F. F. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.27071 · Cited by 50 · see citing works
“For example, ATG5 knockout mice have higher trabecular bone volume compared with the wild‐type 8‐month‐old mice (DeSelm et al., 2011; Xia et al., 2010).”
BackgroundThe osteoblastic niche in the context of multiple myeloma
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Autophagy plays a protective role in cell death of osteoblasts exposure to lead chloride
Lv, X., Zhao, D., Cai, S., Luo, S., You, T., Xu, B., & Chen, K. (2015) · Toxicology Letters · doi:10.1016/j.toxlet.2015.09.014 · Cited by 49 · see citing works
“In addition, AO staining (acidic vesicular organelles) (Xia et al., 2010) and MDC staining (autophagic vacuoles) (Biederbick et al., 1995) demonstrated that autolysosomes were highly accumulated in osteoblasts with treatment of PbCl2 (40 µm/L) for 8 h (Fig.”
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Protective effects of necrostatin-1 on glucocorticoid-induced osteoporosis in rats
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Diabetes Mellitus and Osteoporosis Correlation: Challenges and Hopes
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Modern management of mild autonomous cortisol secretion
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Pravastatin Protects Against Avascular Necrosis of Femoral Head via Autophagy
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“Cells related to bone homeostasis, such as BMSCs, OBs, OCs, and osteocytes,suffering from inactivation or not of autophagy may lead to osteoporosis (Lin et al., 2016; F. Liu, Zhang, Meng, Cai, & Yang, 2017; Luo, Ren, Li, Lian, & Lin, 2016; Ma et al., 2018; Nollet et al., 2014; Xia et al., 2010).”
BackgroundConnexin Gap Junctions and Hemichannels Link Oxidative Stress to Skeletal Physiology and Pathology
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The Impact of Mild Autonomous Cortisol Secretion on Bone Turnover Markers
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Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells
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“This observation was in line with the results of a study by Xia et al (15), which identified that Dex was able to induce autophagy in osteocytes.”
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Evaluation of bone health in patients with adrenal tumors
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Prevention of glucocorticoid induced bone changes with beta-ecdysone
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“We have reported that osteocyte autophagy is crucial to the regulation of bone structure and plays a role in GC induced bone fragility [44,68].”
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“For instance, inhibition of autophagy has been shown to aggravate the effect of glucocorticoid on cell viability of chicken primary osteocytes [59] which may explain the high stress-induced corticosterone levels and osteoporosis in S lines.”
BackgroundREDD1/DDIT4-Independent mTORC1 Inhibition and Apoptosis by Glucocorticoids in Thymocytes
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“Immunoblot analysis showed upregulation of REDD1 in wild-type cells upon dexamethasone treatment, and confirmed that the REDD1(1-65)-b-galactosidase chimeric reporter protein, but not endogenous REDD1 protein, was expressed in the Redd1 cells (Fig.”
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“Many studies have reported that cortisol induces autophagy in osteocytes and T lymphocytes (Jia et al., 2011; Molitoris et al., 2011; Xia et al., 2010).”
BackgroundInfluentialZebrafish as a model to study autophagy and its role in skeletal development and disease
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“Moreover, Dex has been reported to induce apoptosis of osteocytes, as well as inducing autophagy for self-protections (Xia et al., 2010).”
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“Recent studies have revealed that GIOP is closely connected to autophagy and that autophagic flux can influence the occurrence and development of GIOP through osteogenic signalling pathways, thereby regulating the balance between bone resorption and bone formation [41,42].”
BackgroundKar, R., Riquelme, M. A., Hua, R., & Jiang, J. X. (2018) · JBMR Plus · doi:10.1002/jbm4.10077 · Cited by 27 · see citing works
“To elucidate the role of autophagy during oxidant-induced osteocyte death, we either inhibited autophagy by chloroquine or activated autophagy using Dex.”
BackgroundMethodInfluentialLi, C., Yang, P., Liu, B., Bu, J., Liu, H., Guo, J., Hasegawa, T., Si, H., & Li, M. (2021) · Journal of Molecular Histology · doi:10.1007/s10735-021-10006-0 · Cited by 27 · see citing works
- Authors
- Xia, X., Kar, R., Gluhak-Heinrich, J., Yao, W., Lane, N. E., Bonewald, L. F., Biswas, S. K., Lo, W.-K., & Jiang, J. X.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Department of Orthodontics, University of Texas Health Science Center, San Antonio, TX, USA
- University of California Davis Medical Center (US)
- University of Missouri–Kansas City (US)
- Morehouse School of Medicine (US)
- Corresponding author
- Jiang, Jean X
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-10-25
- Volume
- 25
- Issue
- 11
- Pages
- 2479-2488
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- PMC
- PMC3179284
- OpenAlex
- W2004485238
- Cited by
- 193
- References
- 33
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 8 · 2021: 12 · 2020: 12 · 2019: 13 · 2018: 16 · 2017: 11 · 2016: 12 · 2015: 18 · 2014: 22 · 2013: 21 · 2012: 16
- FWCI
- 10.47
- 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, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Tokyo Medical and Dental University
- National Institutes of Health (AQ‐1507, and K24, AR46798)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K24-AR04884, R01AR043052, K24AR048841, P01AR046798, P01AR46798)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12 HD05195801, K12HD051958)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- 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
- Keywords
- glucocorticoids, autophagy, osteocytes, glucocorticoid-induced osteoporosis, autophagosomes, osteocyte viability, autophagy inhibition, TNF-α, apoptosis, bone loss
- MeSH terms
- Adenine, Animals, Autophagy, Cell Count, Cell Line, Chickens, Dexamethasone, Glucocorticoids, Microtubule-Associated Proteins, Osteocytes, Phagosomes, Biomarkers, Apoptosis, Rats
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