Icariin promotes osteogenic differentiation of rat bone marrow stromal cells by activating the ERα-Wnt/β-catenin signaling pathway

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

“…Total flavones of Epimedium (TFE) inhibited reduction of procollagen type I N-terminal propeptide (PINP), and increased serum osteocalcin and type I collagen in OVX rats (13,14). Icariin, one of the major components of Herba Epimedium, decreased activities of serum tartrate-resistant acid phosphatase (TRAP) and bioactive components could stimulate the proliferation, differentiation and mineralization of osteoblasts (12,(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), suppress the adipogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) (41)(42)(43)(44), inhibit the proliferation and differentiation of osteoclasts (45)(46)(47), and induce apoptosis and cell cycle arrest and suppress bone resorption of osteoclasts (48). In addition, icariin was found to significantly attenuate oxidative stress and apoptosis and preserve viability and osteogenic potential of osteoblasts exposed to hypoxia, which indicated that its anti-osteoporotic effect might be attributed to its anti-hypoxic activity (49).…”

“…Taken together, the following pathways were involved in the osteogenesis effect of Herba Epimedium and its constituents: i) activate extracellular-signalregulated kinase (ERK), p38, c-Jun N terminal kinase (JNK)/MAPK pathways in rat BMSCs (50), ii) through ER-mediated ERK and JNK signal activation in MC3T3-E1 osteoblastic cell line (51) (34), vi) involve the ERα-Wnt/β-catenin signaling pathway in rat BMSCs (38), vii) through up-regulation of transforming growth factor (TGF)-β1, BMP2 expression in rabbit BMSCs (30), through up-regulation of BMP2 and Runx2 mRNA expression in calvarial osteoblasts from pups (13), viii) via Notch signaling pathway in rat BMSCs (53), ix) increase OPG and the OPG/RANKL ratio in UMR-106 osteoblastic cells (12), and x) stimulate ER-dependent osteoblastic functions and activate ER in a ligand-independent manner in UMR-106 osteoblastic cells (24,39).…”

New pathway of icariin-induced MSC osteogenesis: transcriptional activation of TAZ/Runx2 by PI3K/Akt

“…Further, they found that several signal molecules downstream of PI3K/Akt, such as eNOS and NO, may play important roles in the differentiation of MSCs. Wei et al found that ERα-Wnt/β-catenin signaling was another pathway involved in the icariin-stimulated osteogenic differentiation of MSCs [13]. The most recent study by Ye et al found that the icariin-induced MSC differentiation was also related to the transcriptional activation of TAZ signaling [10].…”

“…The application of icariin to enhance osteogenic differentiation of MSCs was promising. Previously, several studies have explored the mechanisms of icariin-induced osteogenic differentiation [1,10,13]. In a recent report, a novel mechanism has been revealed in which PI3K/Akt and its downstream pathway played a crucial role in osteogenic differentiation of MSCs induced by icariin [11].…”

Icariin prevents oestrogen deficiency–induced alveolar bone loss through promoting osteogenesis via STAT3

“…Icariin (C 33 H 40 O 15 , ICA) is the major active ingredient of Herba Epimedii and has been proven to be beneficial for bone metabolism in the long bone system . Icariin has been reported to protect against bone loss induced by oestrogen deficiency . Alveolar bone exhibits differences in morphologic features, metabolic rate and pharmaceutical reactions to the long bone system .…”