Morroniside Improves Diabetic Osteoporosis via the AGE/RAGE/Wnt/β-Catenin Signaling Pathway.

Abstract

Morroniside has been shown to possess various pharmacological activities, including anti-inflammatory and antioxidative effects. This study investigates the potential mechanisms by which morroniside ameliorates diabetic osteoporosis (DOP). In vivo experiments were conducted to evaluate biochemical parameters in rats under different treatment conditions. Bone tissues underwent HE staining, and bone mineral density (BMD) along with key bone metabolism markers (β-CTX, OC, SOST) were measured. The activities of antioxidant enzymes (SOD, GPX, CAT), oxidative stress indicators (MDA), and levels of inflammatory factors (MCP-1, IL-6, IL-1, TNF-α) were also assessed. Western blot was used to analyze the expression of proteins associated with AGE/RAGE signaling and the Wnt/β-catenin pathway. Morroniside increased trabecular bone quantity and quality, upregulated the bone formation markers OC and SOST, downregulated the bone resorption marker β-CTX, and significantly increased BMD. Additionally, it modulated the systemic metabolic status by reducing fasting blood glucose (FBG), glycated hemoglobin (HbA1c), free fatty acids (FFA), triglycerides (TG), and total cholesterol (TC). Further research indicated that morroniside inhibited AGE/RAGE signaling, mitigated oxidative stress and inflammatory responses, and enhanced Wnt/β-catenin pathway activity, thereby promoting osteoblast proliferation, differentiation, and mineralization. The introduction of DKK1 significantly attenuated these beneficial effects of morroniside, confirming its protective role through activation of the Wnt/β-catenin pathway. Morroniside exerts beneficial effects on bone metabolism and quality in DOP rats by regulating the AGEs/RAGE/Wnt/β-catenin signaling pathway, while also alleviating oxidative stress and inflammatory responses. These findings provide novel insights and potential therapeutic targets for the treatment of DOP.