Polyphyllin VII attenuated RANKL-induced osteoclast differentiation via inhibiting of TRAF6/c-Src/PI3K pathway and ROS production.
BMC Musculoskelet Disord
; 21(1): 112, 2020 Feb 19.
Article
en En
| MEDLINE
| ID: mdl-32075617
ABSTRACT
BACKGROUND:
Osteoporosis is a worldwide severe bone disease. This study aimed to evaluate the effect of polyphyllin VII on the genesis of osteoclasts from bone marrow macrophages (BMMs) and its potentiality as a therapeutic drug for osteoporosis.METHODS:
BMMs were induced to differentiate into osteoclasts by RANKL and M-CSF. The cells were then treated with various concentrations of polyphyllin VII. Intracellular reactive oxygen species (ROS) measurement assay, resorption pit formation assay, tartrate-resistant acid phosphatase (TRAP) staining and TRAP activity assessment, cell viability assay, active GTPase pull-down assay, immunofluorescent staining, immunoblotting, and RT-PCR were performed.RESULTS:
RANKL + M-CSF significantly increased TRAP activity, number of osteoclasts, number and area of lacunae, intracellular content of ROS, protein levels of Nox1, TRAF6, c-Src and p-PI3K, as well as the content of activated GTP-Rac1, which were significantly blocked by polyphyllin VII in a concentration-dependent manner.CONCLUSION:
These findings suggested that polyphyllin VII inhibited differentiation of BMMs into osteoclasts through suppressing ROS synthesis, which was modulated by TRAF6-cSrc-PI3k signal transduction pathway including GTP-Rac1 and Nox1. Polyphyllin VII could be a therapeutic drug for osteoporosis.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Osteoclastos
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Saponinas
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Genes src
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Especies Reactivas de Oxígeno
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Fosfatidilinositol 3-Quinasas
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Factor 6 Asociado a Receptor de TNF
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Ligando RANK
Límite:
Animals
Idioma:
En
Revista:
BMC Musculoskelet Disord
Asunto de la revista:
FISIOLOGIA
/
ORTOPEDIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China