The Coumarin Derivative 5'-Hydroxy Auraptene Suppresses Osteoclast Differentiation via Inhibiting MAPK and c-Fos/NFATc1 Pathways.
Biomed Res Int
; 2019: 9395146, 2019.
Article
en En
| MEDLINE
| ID: mdl-31976330
ABSTRACT
The phytochemical substances, coumarin derivatives, have demonstrated antiresorptive bone effects by suppressing osteoclast differentiation in vitro and in vivo. Recently, we have identified 5'-hydroxy auraptene (5'-HA), a coumarin derivative isolated from Lotus lalambensis Schweinf, as a novel stimulator for osteoblast differentiation. In this study, we investigated the effect of 5'-HA on osteoclast differentiation of mouse bone marrow (BM) cells. The effect of 5'-HA on BM cell proliferation and osteoclast differentiation was determined by measuring cell viability and tartrate-resistant acid phosphatase (TRAP) enzyme activity, quantification of TRAP+ multinucleated cells (TRAP+MNCs), and quantitative real-time PCR (qPCR) of osteoclastic gene expression. Regulation of NF-κB, c-Fos/NFATc1, and MAPK signaling pathways by 5'-HA during osteoclastogenesis was measured by the NF-κB reporter assay and Western blot analysis. 5'-HA significantly suppresses the receptor activator of NF-κB ligand (RANKL) induced osteoclast differentiation of BM cells in a dose-dependent manner. Consistently, treatment of BM cells with 5'-HA significantly inhibited RANKL-induced activation of NF-κB and c-Fos/NFATc1 pathways in a dose-dependent manner. Furthermore, RANKL-induced phosphorylation of ERK1/2, p-38, and JNK was significantly inhibited by 5'-HA in BM cells. In conclusion, we identified 5'-HA as a novel coumarin derivative that suppresses RANKL-induced osteoclastogenesis via inhibiting c-Fos/NFATc1 and MAPK signaling pathways.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoclastos
/
Diferenciación Celular
/
Proteínas Proto-Oncogénicas c-fos
/
Cumarinas
/
Factores de Transcripción NFATC
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biomed Res Int
Año:
2019
Tipo del documento:
Article
País de afiliación:
Arabia Saudita