HDAC1 overexpression inhibits steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells by inducing SP1 deacetylation.
10.12122/j.issn.1673-4254.2025.01.02
- Author:
Shenyao ZHANG
1
;
Min LU
1
;
Gaoyan KUANG
1
;
Xiaotong XU
1
;
Jun FU
1
;
Churan ZENG
1
Author Information
1. Hunan University of Chinese Medicine, Changsha 410208, China.
- Publication Type:Journal Article
- Keywords:
HDAC1;
SP1;
deacetylation;
steroid-induced osteonecrosis femoral head
- MeSH:
Animals;
Apoptosis/drug effects*;
Mice;
Histone Deacetylase 1/genetics*;
Osteocytes/drug effects*;
Sp1 Transcription Factor/metabolism*;
Acetylation;
Dexamethasone/pharmacology*;
Cell Proliferation/drug effects*;
Caspase 3/metabolism*;
Cell Line;
Hydroxamic Acids/pharmacology*;
bcl-2-Associated X Protein/metabolism*
- From:
Journal of Southern Medical University
2025;45(1):10-17
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:To explore the mechanism by which histone deacetylase 1 (HDAC1) regulates steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells.
METHODS:MLY-O4 cells were treated with 400 nmol/L trichostatin A (TSA) or 1 mmol/L dexamethasone for 24 h or transfected with a HDAC1-overexpressing vector prior to TSA or dexamethasone treatment. The changes in the expressions of HDAC1, SP1, cleaved caspase-3 and Bax, SP1 acetylation level, cell proliferation, and cell apoptosis were examined. The interaction between HDAC1 and SP1 was determined with immunoprecipitation assay and Western blotting.
RESULTS:Treatment with dexamethasone significantly increased cell apoptosis, enhanced the expressions of cleaved caspase-3 and Bax, reduced HDAC1 expression, and suppressed proliferation of MLO-Y4 cells. Both TSA and dexamethasone obviously increased SP1 acetylation level and the expression of SP1 in MLO-Y4 cells. HDAC1 overexpression in the cells significantly attenuated the effect of TSA and dexamethasone, promoted cell proliferation, lowered the expressions of SP1, cleaved caspase-3 and Bax, and inhibited dexamethasone-induced cell apoptosis. Immunoprecipitation assay and Western blotting demonstrated the interaction between HDAC1 and SP1 in the cells.
CONCLUSIONS:HDAC1 inhibits dexamethasone-induced apoptosis and promotes proliferation of cultured mouse osteocytes by suppressing SP1 expression via promoting its deacetylation.
