A Water Extract of Benefiting-Bone Capsule Improves Osteoporosis via Transcriptional and Translational Regulation of Key Factors in Notch and Wnt/β-catenin Signaling Pathways in Ovariectomized Rats

Yingquan Xiong, Hengrui Liu, J

Abstract

Benefiting-Bone Capsule (BBC) is a Chinese herbals formula that shows promise in the treatment and prevention of osteoporosis (OP), but the mechanisms underlying its anti-osteoporotic effects are yet to be established. Here we detect the influence of the extract on several targets of the Notch and Wnt/β- catenin signaling pathways in bone tissue of ovariectomized rats as a model of OP with the aid of realtime PCR, western blot, and immunohistochemical staining. The water extract of BBC exerted a pronounced beneficial effect on OP rats and activated the Wnt/β-catenin pathway through regulating Wnt3a, Wnt10b protein, and glycogen synthesis kinase 3β (GSK-3β) mRNA. Furthermore, the BBC extract inhibited Jagged1, 2 protein and Notch 1,2 mRNA of the Notch signaling pathway. We detected simultaneous changes in the levels of a number of downstream transcripts, including increased runtrelated transcription factor 2 (Runx 2) and decreased peroxisome proliferator-activated receptor γ (PPARγ), which were closely correlated with the treatment effect. Based on the collective findings, we propose that the water extract of BBC regulates OP-associated factors through modulation of key transcripts and proteins in the Notch and Wnt/β-catenin pathways. Our results provide further mechanistic evidence supporting the clinical efficacy of BBC in the treatment of OP.

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