Icariin, a phytoestrogen, exerts rapid estrogenic actions through crosstalk of estrogen receptors in osteoblasts.
Phytother Res
; 37(10): 4706-4721, 2023 Oct.
Article
en En
| MEDLINE
| ID: mdl-37421324
ABSTRACT
Icariin, a flavonoid glycoside derived from Epimedium brevicornum Maxim, exerts bone protective effects via estrogen receptors (ERs). This study aimed to investigate the role of ER-α66, ER-α36, and GPER in bone metabolism in osteoblasts following treatment with icariin. Human osteoblastic MG-63 cells and osteoblast-specific ER-α66 knockout mice were employed. The ERs crosstalk in the estrogenic action of icariin was evaluated in ER-α66-negative human embryonic kidney HEK293 cells. Icariin, like E2, regulated ER-α36 and GPER protein expression in osteoblasts by downregulating them and upregulating ER-α66. ER-α36 and GPER suppressed the actions of icariin and E2 in bone metabolism. However, the in vivo administration of E2 (2 mg/kg/day) or icariin (300 mg/kg/day) restored bone conditions in KO osteoblasts. ER-α36 and GPER expression increased significantly and rapidly activated and translocated in KO osteoblasts after treatment with E2 or icariin. ER-α36 overexpression in KO osteoblasts further promoted the OPG/RANKL ratio induced by E2 or icariin treatment. This study showed icariin and E2 elicit rapid estrogenic responses in bone through recruiting ER-α66, ER-α36, and GPER. Notably, in osteoblasts lacking ER-α66, ER-α36, and GPER mediate the estrogenic effects of icariin and E2, while in intact osteoblasts, ER-α36 and GPER act as negative regulators of ER-α66.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de Estrógenos
/
Fitoestrógenos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Phytother Res
Asunto de la revista:
TERAPIAS COMPLEMENTARES
Año:
2023
Tipo del documento:
Article