Wangbi Tablet Regulates the Osteogenic Homeostasis by MiR335-5p through the Wnt/β-catenin Signaling Pathway and the RANK/RANKL/OPG System: An in Vivo Animal Study

Abstract OBJECTIVE: This study investigated how the classic Chinese patent drug Wangbi tablet (WBT) for treating rheumatoid arthritis (RA) regulates the osteogenic homeostasis through miR335-5p through the Wnt/β-catenin pathway and the RANK/RANKL/OPG system. METHODS: The kidney deficiency pattern modeling rats were established by using castration operation. Collagen-induced arthritis (CIA) was performed on rats for joint modeling. WBT and methotrexate (MTX) gavage interventions were used according to the group situation and body weight. The ankles of the rats were reconstructed in three dimensions using micro-computed tomography (micro-CT). The relative expressions of Wnt3a, Wnt10b, β-catenin, DKK1, RUNX2, DICER1, TRAP6 and NFATC1 in rat ankle bone tissues were measured using Western-Blot (WB). RESULTS: In this study, we found that WBT promoted the expression of Wnt3a, Wnt10b, β-catenin and miR335-5p, decreased the expression of DKK1, promoted the Wnt/β-catenin signalling pathway, increased the expression of osteogenic markers Runx2 and DICER1, and also regulated the RANKL/OPG balance in the affected joint bone tissue. The expression of osteogenic markers TRAP6 and NFATC1 was decreased, and the bone destruction of rats in CIA group and kidney deficiency pattern CIA group was improved. Conclusion: WBT can promote the expression of miR335-5p, inhibit the expression of DKK1, regulate the Wnt/β-catenin signaling pathway and the RANK/RANKL/OPG system in the ankle bone tissue of CIA and kidney deficiency pattern CIA rats, and regulate the balance of osteoclasts to treat bone destruction in RA.