Effect of Quercetin 3-O-β-D-Galactopyranoside on the Adipogenic and Osteoblastogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stromal Cells

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.

The Underlying Mechanism of Chinese Herb of Regulating Marrow in the Treatment of Osteonecrosis of the Femoral Head Based on Network Pharmacology and Molecular Docking

“…Quercetin is one of the natural polyphenols, which widely exists in various plants and was consumed worldwide(18). It has multiple pharmacological effects reported by many studies, such as protecting the bone, reduceing blood glucose, blood pressure, and lipid, and immunomodulatory, anti-in ammatory, and antioxidation activities (19)(20)(21). Wogonin, a compound extracted from the Scutellaria baicalensis plant, exhibits high anti-in ammatory and antioxidative properties, which is achieved reduce expression of transforming growth factor β1 (TGF-β1), high temperature receptor A1 (HTRA1), matrix metalloprotease 13 (MMP-13) and nuclear factor kappa-lightchain-enhancer of activated B cells (NF-κB) (22,23).…”

Purple sweet potato leaf extracts suppress adipogenic differentiation of human bone marrow–derived mesenchymal stem cells

“…Previous studies showed that cyanidin promoted adiponectin expression in 3T3-L1 cells (Matsukawa et al, 2015) and exhibited a protective effect against palmitic acidinduced hypertrophy via PI3K/Akt signaling in 3T3-L1 adipocytes (Molonia et al, 2020). Quercetin is known to suppress adipogenesis in 3T3-L1 cells and MSCs by regulating the AMPK and mitogenactivated protein kinase signaling pathways (Ahn et al, 2008;Oh et al, 2020). Caffeic acid is known to decrease the adipogenesis of 3T3-L1 cells via the induction of AMPK signaling activation (Eid et al, 2017).…”

Dynamic Changes of the Bone Marrow Niche: Mesenchymal Stromal Cells and Their Progeny During Aging and Leukemia

“…Further studies demonstrated that Nestin + MSCs isolated from PTH-treated mice displays enhanced proliferation and differentiation into osteoblasts in culture ( Méndez-Ferrer et al, 2010 ; Ding et al, 2012 ); as well as increased osteogenic differentiation capacity in vivo ( Fan et al, 2017 ). Other studies based on drug screening of natural senolytic substances such as Celastrol and Quercetin 3-O-β-D-galactopyranoside was also shown to promote osteogenesis and inhibit adipogenesis in vitro through PGC-1α signaling ( Li et al, 2020 ; Oh et al, 2020 ). On a similar note, inhibition of the mTOR-pathway was shown to extensively prolong life-span in mice ( Papadopoli et al, 2019 ), including revitalized pluripotency of human MSCs in vitro ( Antonioli et al, 2019 ).…”