Effects of naringin on the proliferation and osteogenic differentiation of human amniotic fluid-derived stem cells

Abstract

Human amniotic fluid-derived stem cells (hAFSCs) are a novel cell source for generating osteogenic cells to treat bone diseases. Effective induction of osteogenic differentiation from hAFSCs is critical to fulfil their therapeutic potential. In this study, naringin, the main active compound of Rhizoma drynariae (a Chinese herbal medicine), was used to stimulate the proliferation and osteogenic differentiation of hAFSCs. The results showed that naringin enhanced the proliferation and alkaline phosphatase activity (ALP) of hAFSCs in a dose-dependent manner in the range 1-100 µg/ml, while an inhibition effect was observed at 200 µg/ml. Consistently, the calcium content also increased with naringin concentration up to 100 µg/ml. The enhanced osteogenic differentiation of hAFSCs by naringin was further confirmed by the dose-dependent upregulation of marker genes, including osteopontin (OPN) and Collagen I from RT-PCR analysis. The increased osteoprotegerin (OPG) expression and minimal expression of receptor activator of nuclear factor-κB ligand (RANKL) suggested that naringin also inhibited osteoclastogenesis of hAFSCs. In addition, the gene expressions of bone morphogenetic protein 4 (BMP4), runt-related transcription factor 2 (RUNX2), β-catenin and Cyclin D1 also increased significantly, indicating that naringin promotes the osteogenesis of hAFSCs via the BMP and Wnt-β-catenin signalling pathways. These results suggested that naringin can be used to upregulate the osteogenic differentiation of hAFSCs, which could provide an attractive and promising treatment for bone disorders. Copyright © 2014 John Wiley & Sons, Ltd.

Protective effect of naringin against ankylosing spondylitis via ossification, inflammation and oxidative stress in mice

“…The present study showed that administration of naringin increased OC and ALP activity, while reducing TG activity in AS model mice. These results are consistent with those of previous studies; for example, Liu et al suggested that the effects of naringin upregulates osteogenesis in human amniotic fluid-derived stem cells (22). Furthermore, Li et al reported that naringin is able to significantly improved ALP activity as well as upregulate the expression of type I collagen in the osteoblastic cell line MC3T3-E1 (23).…”

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

“…Rhizoma Drynariae and its bioactive constituents were able to promote the osteoblastic proliferation, differentiation, and maturation (56,58,59,(62)(63)(64)(65)(66)(67)(68)(69)(70), inhibit osteoblastic apoptosis (71), suppress osteoclastogenesis (72)(73)(74), promote the apoptosis of osteoclasts (60), stimulate both cellular and humoral immunity (75), and inhibit cathepsins K processing (76,77).…”

“…Mechanisms involved in the osteogenesis and osteolysis effect of Rhizoma Drynariae and its components included: i) promote proliferation, differentiation, and maturation of rat calvarial osteoblasts (64) and UMR-106 osteoblastic cells (58,68) via ER pathway, ii) promote osteoblastogenesis from rat BMSCs via the Notch signaling pathway (70), iii) inhibit osteoclastogenesis of human amniotic fluid-derived stem cells (hAFSCs) via elevating OPG/RANKL ratio and induce the osteogenesis of hAFSCs via the BMP and Wnt/β-catenin pathways (72), and iv) promote the apoptosis of osteoclasts by regulating the mitochondrial apoptosis pathway using RAW 264.7 cells (60).…”

Osteogenic differentiation of amniotic fluid mesenchymal stromal cells and their bone regeneration potential

“…Herbal medicines have also been used to improve the osteogenic differentiation of AFMSCs. Naringin, the main active compound of Chinese herbal medicine (Rhizoma drynariae), proved able to enhance osteo genic differentiation, increasing ALP activity and the expression of the osteogenic specific markers OPN, Collagen I, bone morphogenetic protein 4 (BMP4), RUNX2, βcatenin and cyclin D1 [66] . Another traditional Chinese herbal medicine commonly used in treating orthopedic disorders, Curculi goside, was found to have a positive effect on the osteogenic differentiation of human AFSCs [65] .…”