12-Deoxyphorbol 13-acetate inhibits RANKL-induced osteoclastogenesis via the attenuation of MAPK signaling and NFATc1 activation.
Int Immunopharmacol
; 101(Pt A): 108177, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34626872
ABSTRACT
Osteoporosis, characterized by bone loss and microstructure damage, occurs when osteoclast activity outstrips osteoblast activity. Natural compounds with inhibitory effect on osteoclast differentiation and function have been evidenced to protect from osteoporosis. After multiple compounds screening, 12-deoxyphorbol 13-acetate (DPA) was found to decline RANKL-induced osteoclastogenesis dose-dependently by attenuating activities of NFATc1 and c-Fos, followed by decreasing the level of osteoclast function-associated genes and proteins including Acp5, V-ATPase-d2 and CTSK. Mechanistically, we found that DPA suppressing RANKL-induced downstream signaling pathways, including MAPK signaling pathway and calcium oscillations. Furthermore, the in vivo efficacy of DPA was further confirmed in an OVX-induced osteoporosis mice model. Collectively, the results in our presentation reveal that DPA might be a promising compound to manage osteoporosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoporose
/
Ésteres de Forbol
/
Fatores de Transcrição NFATC
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China