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

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.