BASP1 down-regulates RANKL-induced osteoclastogenesis.
Exp Cell Res
; 431(1): 113758, 2023 10 01.
Article
em En
| MEDLINE
| ID: mdl-37619639
ABSTRACT
The cytokine RANKL (Receptor Activator of NFκB Ligand) is the key driver of differentiation of monocytes/macrophages to form multi-nucleated, bone-resorbing osteoclasts, a process that is accompanied by significant changes in gene expression. We show that exposure to RANKL rapidly down-regulates expression of Brain Acid Soluble Protein 1 (BASP1) in cultured primary mouse bone marrow macrophages (BMMs), and that this reduced expression is causally linked to the osteoclastogenic process in vitro. Knocking down BASP1 expression in BMMs or eliminating its expression in these cells or in RAW 264.7 cells enhanced RANKL-induced osteoclastogenesis, promoted cell-cell fusion, and generated cultures containing larger osteoclasts with increased mineral degrading abilities relative to controls. Expression of exogenous BASP1 in BMMs undergoing osteoclastogenic differentiation produced the opposite effects. Upon exposure to RANKL, primary mouse BMMs in which BASP1 had been knocked down exhibited increased expression of the key osteoclastogenic transcription factor Nfatc1and of its downstream target genes Dc-stamp, Ctsk, Itgb3, and Mmp9 relative to controls. The knock-down cells also exhibited increased sensitivity to the pro-osteoclastogenic effects of RANKL. We conclude that BASP1 is a negative regulator of RANKL-induced osteoclastogenesis, which down-regulates the pro-osteoclastogenic gene expression pattern induced by this cytokine. Decreased expression of BASP1 upon exposure of BMMs to RANKL removes a negative regulator of osteoclastogenesis and promotes this process.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
/
Fatores de Transcrição
Limite:
Animals
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2023
Tipo de documento:
Article