» Articles » PMID: 37365870

Galangin Mitigates Glucocorticoid-induced Osteoporosis by Activating Autophagy of BMSCs Via Triggering the PKA/CREB Signaling Pathway

Overview
Authors
Affiliations
Soon will be listed here.
Abstract

Glucocorticoid-induced osteoporosis (GIOP), one of the most common and serious adverse effects associated with glucocorticoid administration, manifests as decreased bone formation and increased bone resorption, eventually culminating in bone loss. Galangin (GAL) is a flavonoid extracted from the medicinal herbal galangal that possesses a variety of pharmacological activities and can inhibit osteoclastogenesis. However, the effects of GAL on GIOP remain unclear. Our study aims to explore the effects of GAL on GIOP in mice and the underlying mechanism. Our results show that GAL markedly mitigates the severity of dexamethasone (Dex)-induced osteoporosis in mice and potentiates osteogenic differentiation in mouse bone marrow-derived mesenchymal stem cells (BMSCs). Furthermore, GAL also significantly counteracts Dex-mediated suppression of osteogenic differentiation and autophagy in human BMSCs. GAL augments PKA/CREB-mediated autophagic flux in BMSCs and the bones of osteoporotic mice. GAL-mediated osteogenic differentiation in Dex-treated BMSCs is significantly decreased by the PKA inhibitor H89 and autophagy inhibitor 3-methyladenine. Collectively, our data indicate that GAL can ameliorate GIOP, partly by augmenting the mineralization of BMSCs by potentiating PKA/CREB-mediated autophagic flux, highlighting its potential therapeutic use in treating glucocorticoid-related osteoporosis.

Citing Articles

Bioactive Compounds from Propolis on Bone Homeostasis: A Narrative Review.

Bertolucci V, Ninomiya A, Longato G, Kaneko L, Nonose N, Scariot P Antioxidants (Basel). 2025; 14(1).

PMID: 39857415 PMC: 11762496. DOI: 10.3390/antiox14010081.


KLF7 reverses ox-LDL-induced ferroptosis in HMEC-1 cells through transcriptionally activating ALKBH5 to inhibit the m6A modification of ACSL4.

Xiong Q, Luo Z, Xie X, Zhou W Cytotechnology. 2024; 76(6):653-666.

PMID: 39435423 PMC: 11490622. DOI: 10.1007/s10616-024-00641-2.


Loss of BACH1 improves osteogenic differentiation in glucocorticoid-induced hBMSCs through restoring autophagy.

Xiao S, Li G, Tan M, Liu W, Li W BMC Musculoskelet Disord. 2024; 25(1):665.

PMID: 39182017 PMC: 11344390. DOI: 10.1186/s12891-024-07761-y.


Galangin: A Promising Flavonoid for the Treatment of Rheumatoid Arthritis-Mechanisms, Evidence, and Therapeutic Potential.

Khawaja G, El-Orfali Y, Shoujaa A, Abou Najem S Pharmaceuticals (Basel). 2024; 17(7).

PMID: 39065811 PMC: 11279697. DOI: 10.3390/ph17070963.


Lithium prevents glucocorticoid-induced osteonecrosis of the femoral head by regulating autophagy.

Wang Q, Yang Z, Li Q, Zhang W, Kang P J Cell Mol Med. 2024; 28(10):e18385.

PMID: 38801405 PMC: 11129728. DOI: 10.1111/jcmm.18385.


References
1.
Zhong M, Huang Y, Zeng B, Xu L, Zhong C, Qiu J . Induction of multiple subroutines of regulated necrosis in murine macrophages by natural BH3-mimetic gossypol. Acta Biochim Biophys Sin (Shanghai). 2022; 54(1):64-76. PMC: 9909304. DOI: 10.3724/abbs.2021004. View

2.
DArcy M . A review of biologically active flavonoids as inducers of autophagy and apoptosis in neoplastic cells and as cytoprotective agents in non-neoplastic cells. Cell Biol Int. 2022; 46(8):1179-1195. DOI: 10.1002/cbin.11813. View

3.
Wang L, Heckmann B, Yang X, Long H . Osteoblast autophagy in glucocorticoid-induced osteoporosis. J Cell Physiol. 2018; 234(4):3207-3215. DOI: 10.1002/jcp.27335. View

4.
Li M, Xie Z, Li J, Lin J, Zheng G, Liu W . GAS5 protects against osteoporosis by targeting UPF1/SMAD7 axis in osteoblast differentiation. Elife. 2020; 9. PMC: 7609060. DOI: 10.7554/eLife.59079. View

5.
Wang J, Liu B, Xu Y, Yang M, Wang C, Song M . Activation of CREB-mediated autophagy by thioperamide ameliorates β-amyloid pathology and cognition in Alzheimer's disease. Aging Cell. 2021; 20(3):e13333. PMC: 7963336. DOI: 10.1111/acel.13333. View