Formononetin attenuates osteoclast differentiation and calcium loss by mediating transcription factor AP-1 in type I diabetic mice

芒柄花素通过介导转录因子 AP-1 减轻 I 型糖尿病小鼠破骨细胞分化和钙流失

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作者:Wensen Jing, Lei Feng, Kan Peng, Weisong Zhang, Bo Wang

Abstract

Formononetin (FMN) has been reported as a prospective antiosteoporotic medication. However, the antiosteoporotic properties of FMN are still unclear in a mouse model with diabetes-induced osteoporosis. An osteoporotic or osteopenic mouse model with type I diabetes mellitus (T1DM) was established using streptozotocin (40 mg/kg) injection for 5 consecutive days. After 12 weeks with FMN intragastric administration (0.5, 5, 20 mg/kg), the antiosteoporotic activity of FMN was evaluated in T1DM mice. FMN supplementation effectively improves Ca excretion and trabecular bone degeneration and impedes osteoclast differentiation and function to attenuate hyperglycemia-induced bone deterioration. In addition, FMN inhibited activating protein 1 (AP-1) and osteoclast-specific gene expression, Nfatc1, Ctsk, and TRAP. The administration of FMN has a beneficial effect to attenuate hyperglycemia-induced bone deteriorations, including osteoclastogenesis, trabecular bone, and Ca loss. Our study provided a prospective medication for the treatment of T1DM-related osteopenia or osteoporosis with FMN.

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