title: Effects of quercetin, a natural phenolic compound, in the differentiation of human mesenchymal stem cells (MSC) into adipocytes and osteoblasts.
abstract: Natural phenols may have beneficial properties against oxidative stress, which is associated with aging and major chronic aging-related diseases, such as loss of bone mineral mass (osteoporosis) and diabetes. The main aim of this study was to analyze the effect of quercetin, a major nutraceutical compound present in the "Mediterranean diet", on mesenchymal stem-cell (MSC) differentiation. Such cells were induced to differentiate into osteoblasts or adipocytes in the presence of two quercetin concentrations (0.1 and 10μM). Several physiological parameters and the expression of osteoblastogenesis and adipogenesis marker genes were monitored. Quercetin (10μM) inhibited cell proliferation, alkaline phosphatase (ALPL) activity and mineralization, down-regulating the expression of ALPL, collagen type I alpha 1 (COL1A1) and osteocalcin [bone gamma-carboxyglutamate protein (BGLAP)] osteoblastogenesis-related genes in MSC differentiating into osteoblasts. Moreover, in these cultures, CCAAT/enhancer-binding protein alpha (CEBPA) and peroxisome proliferator-activated receptor gamma 2 (PPARG2) adipogenic genes were induced, and cells differentiated into adipocytes were observed. Quercetin did not affect proliferation, but increased adipogenesis, mainly at 10-μM concentration in MSC induced to differentiate to adipocytes. β- and γ-catenin (plakoglobin) nuclear levels were reduced and increased, respectively, in quercetin-treated cultures. This suggests that the effect of high concentration of quercetin on MSC osteoblastic and adipogenic differentiation is mediated via Wnt/β-catenin inhibition. In conclusion, quercetin supplementation inhibited osteoblastic differentiation and promoted adipogenesis at the highest tested concentration. Such possible adverse effects of high quercetin concentrations should be taken into account in nutraceutical or pharmaceutical strategies using such flavonol.
authors.affiliation: Unidad de Metabolismo Mineral, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Casado-Díaz
authors.affiliation: Departamento de Genética, Universidad de Córdoba, Campus Rabanales, 14071 Córdoba, Spain.
authors.forename: Jaouad
authors.initials: J
authors.lastname: Anter
authors.affiliation: Dep. Bioquímica y Biología Molecular, Campus de Rabanales C6-1-E17, Campus de Excelencia Internacional Agroalimentario, Universidad de Córdoba, 14071 Córdoba, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Dorado
authors.affiliation: Unidad de Metabolismo Mineral, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain. Electronic address: md1qugoj@uco.es.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Quesada-Gómez
mesh_terms: D052438:Adipocytes, White / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis; D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D000090602:Collagen Type I, alpha 1 Chain; D019587:Dietary Supplements; D015536:Down-Regulation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D011794:Quercetin / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000975:Antioxidants; D015415:Biomarkers; C000716127:COL1A1 protein, human; D000090602:Collagen Type I, alpha 1 Chain; D017382:Reactive Oxygen Species; D011794:Quercetin
keywords: Adipogenesis; Beta-catenin; Gamma-catenin; Mesenchymal stem cells; Osteoblastogenesis; Quercetin