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Glucocorticoid-induced autophagy and apoptosis in bone

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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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