Tricin protects rats from ovariectomized-induced osteoporosis by enhancing Wnt/β-catenin pathway

Abstract

Purpose: To investigate the effects of tricin on ovariectomized-induced osteoporosis, and unravel theunderling mechanism of action.Methods: An osteoporosis rat model was established by conducting ovariectomy (OVX). Changes in the microstructure of the trabecular bone were visualized using Hematoxylin and eosin (H&E) staining, and a three-point bending test was employed to assess the biomechanical stability of the femurs, after the administration of tricin (20 and 40 mg/kg). Subsequently, bone marrow mesenchymal stem cells (BMSCs) were isolated and treated with tricin (7 and 15 μM). Alizarin red staining was performed to assess mineralization, and Runt-related transcription factor 2 (RUNX2); osteocalcin (OCN) and collagen type I alpha 1 (Col1a1) were quantified using western blot analysis. The Wnt/β-catenin pathway related proteins, i.e., Wnt3a, β-catenin, glycogen synthase kinase-3 β (GSK-3 β) were determined.Results: Ovariectomy induced thinner and discontinuous trabecular bone, with increased marrow cavities, while application of tricin significantly improved the density and regularity meshwork, but reduced marrow cavities. Tricin also enhanced biomechanical competence as seen in the upregulated maximum load, stiffness, young modulus and maximum stress compared with OVX group (p < 0.01). Furthermore, tricin increased calcification in BMSCs, and significantly upregulated the expressions of RUNX2, OCN and COL1A1 when compared with OVX group (p < 0.01). It promoted Wnt/β-catenin signaling by enhancing Wnt3a and β-catenin, while inhibiting GSK3β expression, compared with OVX group (p < 0.05 or p < 0.01).Conclusion: Tricin exerts protective effects against OVX-induced osteoporosis by enhancing Wnt/β-catenin pathway. Thus, tricin is a potential therapeutic agent for the management of osteoporosis.