Antiosteoporotic effect of icariin in ovariectomized rats is mediated via the Wnt/β-catenin pathway

Abstract

Icariin (ICA), the main active flavonoid glucoside isolated from Herba Epimedii, has been shown to prevent postmenopausal bone loss in vitro. However, the mechanisms by which ICA prevents bone loss in vivo remain poorly understood. In the present study, the effect of ICA in an ovariectomized (OVX) rat model of osteoporosis was evaluated. Sprague-Dawley rats were divided into sham-operated and OVX groups. The OVX rats were randomly divided into five groups: OVX group (water only), Fosamax (positive) group (5.04 mg/kg, weekly, administered orally), and OVX-ICA groups (125, 250 or 500 mg/kg, daily, administered orally) and treated for 12 weeks. The 125, 250 and 500 mg/kg doses of ICA were designated as low (L-ICA), medium (M-ICA) and high (H-ICA), respectively. Compared with the sham-operated group, the OVX rats had significantly decreased bone mineral density (BMD), reduced serum osteoprotegerin (OPG) and increased serum bone gla protein (BGP) concentrations. ICA significantly increased BMD, biomechanical strength, trabecular bone number and trabecular bone thickness, and reduced lumbar trabecular bone separation. Treatment with ICA also completely normalized the expression of osteoblast markers by increasing serum concentrations of OPG and BGP. Enhanced mineralization was demonstrated by increased expression of differentiation markers. Although further in vivo studies are required to investigate the efficacy of ICA in improving bone mass, this study demonstrates that ICA has strong osteogenic activity, inducing osteogenic differentiation and inhibiting resorption by osteoclasts. It also demonstrates an antiosteoporotic effect for ICA on the basis of BMD, biochemical markers, biomechanical tests and histopathological parameters. Compared with L-ICA and H-ICA, M-ICA was more effective and caused no liver or kidney damage.

Chinese single herbs and active ingredients for postmenopausal osteoporosis: From preclinical evidence to action mechanism

“…FE increased OPG protein expression and reduced the RANKL protein expression in OVX rats (18). Icariin increased the mRNA expression ratio of OPG/RANKL, up-regulated mRNA expression of low-density lipoprotein receptorrelated protein 6 (Lrp6) receptor, while it downregulated glycogen synthase kinase-3β and Runx2, following OVX (24,25). Icariin was also found to upregulate expression of bone morphogenetic protein 2 (BMP2), BMP4, Runx2, osteocalcin, Wnt1, and Wnt3a in OPG knockout mice, and increase the expression of the direct target genes of β-catenin signaling such as AXIN2, dickkopf-related protein 1 (DKK1), T cell factor 1 (TCF1), and lymphoid enhancer-binding factor 1 (LEF1) (26).…”

The Combination of icariin and constrained dynamic loading stimulation attenuates bone loss in ovariectomy‐induced osteoporotic mice

“…Moreover, icariin inhibited osteoclast differentiation and bone resorption by suppression of MAPKs/ NF‐κB . The recent study showed that icariin has strong osteogenic activity, inducing osteogenic differentiation and inhibiting resorption by osteoclasts in ovariectomized rats …”

Integration of summary data from GWAS and eQTL studies identified novel causal BMD genes with functional predictions

“…In the ASB16-AS1 centered network, gene CTNNB1 encodes β-catenin protein which can aggregate and move into the nucleus and then can active wnt/β-catenin signaling pathway. The target gene of β-catenin protein, RUNX2 , is active to promote osteoblast proliferation and differentiation [51–53]. Interestingly, these genes which mainly play roles in osteoblasts, were found to be co-expressed with ASB16-AS1 in PBMs which are precursors of osteoclasts [33].…”