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Lithium prevents glucocorticoid-induced osteonecrosis of the femoral head by regulating autophagy.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2024 May; Vol. 28 (10), pp. e18385. - Publication Year :
- 2024
-
Abstract
- Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC-ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC-ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC-induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC-ONFH was used for evaluating the therapeutic effect of oral lithium on GC-ONFH and underlying mechanism. Findings demonstrated that GC over-activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over-activated autophagy of GC-treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC-ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over-activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up-regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC-ONFH. Lithium may be a promising therapeutic agent for GC-ONFH. However, the role of autophagy in the pathogenesis of GC-ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC-ONFH, and the efficacy of lithium in the treatment of GC-ONFH and its underlying mechanisms.<br /> (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Subjects :
- Animals
Rats
Male
Osteogenesis drug effects
Rats, Sprague-Dawley
Proto-Oncogene Proteins c-akt metabolism
Disease Models, Animal
Phosphatidylinositol 3-Kinases metabolism
Femur Head pathology
Femur Head drug effects
Femur Head metabolism
Osteonecrosis chemically induced
Osteonecrosis pathology
Osteonecrosis drug therapy
Osteonecrosis metabolism
Osteonecrosis prevention & control
Autophagy drug effects
Glucocorticoids pharmacology
Glucocorticoids adverse effects
Femur Head Necrosis chemically induced
Femur Head Necrosis pathology
Femur Head Necrosis drug therapy
Femur Head Necrosis metabolism
TOR Serine-Threonine Kinases metabolism
Signal Transduction drug effects
Lithium pharmacology
Osteoblasts drug effects
Osteoblasts metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 28
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 38801405
- Full Text :
- https://doi.org/10.1111/jcmm.18385