Abstract
Glucocorticoids are widely prescribed to treat various allergic and autoimmune diseases; however, long-term use results in glucocorticoid-induced osteoporosis, characterized by consistent changes in bone remodeling with decreased bone formation as well as increased bone resorption. Not only bone mass but also bone quality decrease, resulting in an increased incidence of fractures. The primary role of autophagy is to clear up damaged cellular components such as long-lived proteins and organelles, thus participating in the conservation of different cells. Apoptosis is the physiological death of cells, and plays a crucial role in the stability of the environment inside a tissue. Available basic and clinical studies indicate that autophagy and apoptosis induced by glucocorticoids can regulate bone metabolism through complex mechanisms. In this review, we summarize the relationship between apoptosis, autophagy and bone metabolism related to glucocorticoids, providing a theoretical basis for therapeutic targets to rescue bone mass and bone quality in glucocorticoid-induced osteoporosis.
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Abbreviations
- 3-MA:
-
3-Methyladenine
- 11β-HSD2:
-
11β-Hydroxysteroid dehydrogenase type 2
- AS:
-
Ankylosing spondylitis
- ATG:
-
Autophagy-related gene
- Becn1:
-
Beclin 1
- BMSCs:
-
Bone mesenchymal stem cells
- BALP:
-
Bone-specific alkaline phosphatase
- CTSK:
-
Cathepsin K
- CQ:
-
Chloroquine
- Cx:
-
Connexins
- ECM:
-
Extracellular matrix
- ERK:
-
Extracellular signal-regulated kinase
- FAKs:
-
Focal adhesion kinases
- FoxO:
-
Forkhead box O
- GIOP:
-
GC-induced osteoporosis
- GCs:
-
Glucocorticoids
- GR:
-
Glucocorticoid receptor
- GSK-3:
-
Glycogen synthase kinase 3
- HMGB1:
-
High mobility group box 1
- HIFα:
-
Hypoxia-inducible factor α
- IGF:
-
Insulin-like growth factors
- IL:
-
Interleukin
- JNK:
-
C-Jun N-terminal kinase
- LC3-II:
-
LC3-PE
- LRP:
-
Low-density lipoprotein receptor-related protein
- M-CSF:
-
Macrophage colony stimulating factor
- mTOR:
-
Mammalian target of rapamycin
- MCPIP:
-
MCP-induced protein 1
- NFATC1:
-
Nuclear factor of activated t cells 1
- OPG:
-
Osteoprotegerin
- PPAR-γ:
-
Peroxisome proliferator-activated receptor gamma
- PGE2:
-
Prostaglandin E2
- PE:
-
Phosphatidyl ethanolamine
- PI3K:
-
Phosphatidylinositol-kinase, phosphatidyl-inositol-3-kinase
- NAC:
-
N-Acetyl-cysteine
- RANKL:
-
Receptor activator of nuclear factor kappa-B ligand
- Runx2:
-
Runt-related transcription factor 2
- Pyk2:
-
Proline-rich tyrosine kinase 2
- Panx1:
-
Pannexin-1
- ROS:
-
Reactive oxygen species
- Vps34:
-
Vacuolar protein sorting
- RA:
-
Rheumatoid arthritis
- TRAP:
-
Tartrate-resistant acid phosphatase
- TMP:
-
Tetramethylpyrazine
- (TNF)-α:
-
Tumor necrosis factor
- TRAIL:
-
TNF-related apoptosis-inducing ligand
- TRAF3:
-
TNF receptor-associated factor 3
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Acknowledgements
This work was supported by Grants from National Natural Science Foundation of China (81572236 to C.Q. He), the Chengdu Bureau of Science and Technology (No. 2015-HM02-00042-SF to C.Q. He) and Sichuan Science and Technology (No. 2015SZ0054 to C.Q. He).
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Tiantian Wang, Xiaonan Liu and Chengqi He declare that they have no conflict of interest.
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Wang, T., Liu, X. & He, C. Glucocorticoid-induced autophagy and apoptosis in bone. Apoptosis 25, 157–168 (2020). https://doi.org/10.1007/s10495-020-01599-0
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DOI: https://doi.org/10.1007/s10495-020-01599-0