Icariin Regulates the Bidirectional Differentiation of Bone Marrow Mesenchymal Stem Cells through Canonical Wnt Signaling Pathway

Abstract

Fat infiltration within the bone marrow is easily observed in some postmenopausal women. Those fats are mainly derived from bone marrow mesenchymal stem cells (BMMSCs). The increment of adipocytes derived from BMMSCs leads to decreased osteoblasts derived from BMMSCs, so the bidirectional differentiation of BMMSCs significantly contributes to osteoporosis. Icariin is the main extractive of Herba Epimedii which is widely used in traditional Chinese medicine. In this experiment, we investigated the effect of icariin on the bidirectional differentiation of BMMSCs through quantitative real-time PCR, immunofluorescence, western blot, and tissue sections in vitro and in vivo. We found that icariin obviously promotes osteogenesis and inhibits adipogenesis through detecting staining and gene expression. Micro-CT analysis showed that icariin treatment alleviated the loss of cancellous bone of the distal femur in ovariectomized (OVX) mice. H&E staining analysis showed that icariin-treated OVX mice obtained higher bone mass and fewer bone marrow lipid droplets than OVX mice. Western blot and immunofluorescence showed that icariin regulates the bidirectional differentiation of BMMSCs via canonical Wnt signaling. This study demonstrates that icariin exerts its antiosteoporotic effect by regulating the bidirectional differentiation of BMMSCs through the canonical Wnt signaling pathway.

Icariin promotes osteogenic differentiation of bone marrow stromal cells and prevents bone loss in OVX mice via activating autophagy

“…Icariin (ICA, C 33 H 40 O 15 , molecular weight: 676.67) is a natural flavonoid glycoside isolated from Herba Epimedii, which is used in traditional Chinese medicine for treatment of kidneys, joints, and other disorders . ICA has been shown to prevent ovariectomy (OVX)‐induced bone loss and it restored femoral strength in ovariectomized rats …”

Polyphenols from grape pomace induce osteogenic differentiation in mesenchymal stem cells

“…In particular, the BMP2 and Runx2 increase was shown to be induced by Arneis PRPE, which is particularly rich in the flavonoid glycoside rutin. Flavonoid glycosides have been shown to possess a high osteogenic potential related to the stimulation of BMP2 and Runx2 expression (62)(63)(64)(65)(66)(67). More generally, polyphenols are able to enhance osteoblast activity and differentiation, by targeting Runx2 through different signaling pathways (16,50,(68)(69)(70) and by inducing the expression of bone-matrix related genes (71)(72)(73)(74).…”

Icaritin promotes the osteogenesis of bone marrow mesenchymal stem cells via the regulation of sclerostin expression

“…The results of the present study demonstrated that the small phytomolecule icaritin enhanced osteogenic differentiation of hBMScs in vitro, with the greatest effect demonstrated These results suggest that SOST is a key factor in the icaritin-mediated osteogenesis of hBMScs. Herba epimedii is used for curing bone-associated disorders in china (10). Icariin is considered to be the major pharmacologically active component and it promotes osteogenesis of hBMScs (10).…”

“…Icariin, extracted from Herba epimedii, has been suggested to significantly improve osteogenesis to decrease bone loss in ovariectomized rats and steroid-induced osteonecrosis of the femoral head (10). However, recent studies have demonstrated that icariin is enzymatically hydrolyzed, and then subsequently metabolized to desmethyl icaritin and icaritin; desmethyl icaritin is suggested to have more potent pharmacological effects compared with icariin (11,12).…”

“…The osteogenic effects of icaritin have been clearly described, but the underlying mechanisms remain unclear. As icaritin has been suggested to regulate the Wnt/β-catenin pathway (10) and ERα (9), which are closely associated with SOST, we hypothesized that icaritin may promote osteogenesis through inhibiting SOST.…”