Abstract
Natural products, especially phenols, are promising therapeutic agents with beneficial effects against aging-related complications such as osteoporosis. This study aimed to investigate the effect of quercetin 3-O-β-D-galactopyranoside (Q3G), a glycoside of a common bioactive phytochemical quercetin, on osteogenic and adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). hBM-MSCs were induced to differentiate into osteoblasts and adipocytes in the presence or absence of Q3G and the differentiation markers were analyzed to observe the effect. Q3G treatment stimulated the osteoblastogenesis markers: cell proliferation, alkaline phosphatase (ALP) activity and extracellular mineralization. In addition, it upregulated the expression of RUNX2 and osteocalcin protein as osteoblastogenesis regulating transcription factors. Moreover, Q3G treatment increased the activation of osteoblastogenesis-related Wnt and bone morphogenetic protein (BMP) signaling displayed as elevated levels of phosphorylated β-catenin and Smad1/5 in nuclear fractions of osteo-induced hBM-MSCs. The presence of quercetin in adipo-induced hBM-MSC culture inhibited the adipogenic differentiation depicted as suppressed lipid accumulation and expression of adipogenesis markers such as PPARγ, SREBP1c and C/EBPα. In conclusion, Q3G supplementation stimulated osteoblast differentiation and inhibited adipocyte differentiation in hBM-MSCs via Wnt/BMP and PPARγ pathways, respectively. This study provided useful information of the therapeutic potential of Q3G against osteoporosis mediated via regulation of MSC differentiation.
Highlights
Osteoporosis is a common medical condition in which bone formation becomes imbalanced, and the bone is filled with adipocytes rather than osteoblasts [1]
The current study evaluated the effect of a quercetin glycoside, quercetin 3-O-β-D-galactopyranoside (Q3G), on the adipogenic and osteogenic differentiation of hBM-mesenchymal stem cells (MSCs) in order to provide insights for its anti-osteoporotic potential
It has been shown that quercetin has a beneficial effect on bone resorption, osteogenic differentiation and overall bone repair mechanisms [19,20]
Summary
Osteoporosis is a common medical condition in which bone formation becomes imbalanced, and the bone is filled with adipocytes rather than osteoblasts [1]. This imbalance in the bone mass manifests as increased fragility and prone to fractures. The reciprocal relationship between the adipogenesis and osteoporosis of MSCs makes inducing MSCs in favor of osteoblastogenesis to increase bone mass a promising therapeutic target for osteoporosis treatment. Studies have identified two pathways that regulate MSC differentiation where one is activated, the other is suppressed: peroxisome proliferator-activated receptor γ (PPARγ) and Wnt/β-catenin signaling [4]. Inducing MSCs to differentiate into adipocytes through PPARγ activation inhibits the bone morphogenetic protein (BMP)-induced osteoblastogenesis and vice versa
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