title: Sulfuretin induces osteoblast differentiation through activation of TGF-β signaling.
abstract: The identification and examination of potential determinants controlling the progression of cell fate toward osteoblasts can be intriguing subjects. In this study, the effects of sulfuretin, a major compound isolated from Rhus verniciflua Stokes, on osteoblast differentiation were investigated. Treatments of sulfuretin induced alkaline phosphatase (ALP) activity in mesenchymal C3H10T1/2 cells and mineralization in preosteoblast MC3T3-E1 cells. Pro-osteogenic effects of sulfuretin were consistently observed in freshly isolated primary bone marrow cells. In mechanical studies, sulfuretin specifically induced expression of TGF-β target genes, such as SMAD7 and PAI-1, but not other signaling pathway-related genes. Similar to the results of gene expression analysis, reporter assays further demonstrated TGF-β-specific induction by sulfuretin. Furthermore, disruption of TGF-β signaling using treatment with TGF-β-specific inhibitor, SB-431542, and introduction of SMAD2/3 small interfering RNA impaired the effects of sulfuretin in inducing ALP activity and expression of ALP mRNA. Together, these data indicate that the pro-osteogenic effects of sulfuretin are mediated through activation of TGF-β signaling, further supporting the potential of sulfuretin in the prevention of bone-related diseases such as bone fracture and osteoporosis.
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: No-Joon
authors.initials: NJ
authors.lastname: Song
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: So-Mi
authors.initials: SM
authors.lastname: Kwon
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Suji
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Hyang-Jin
authors.initials: HJ
authors.lastname: Yoon
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Cho-Rong
authors.initials: CR
authors.lastname: Seo
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Byunghyun
authors.initials: B
authors.lastname: Jang
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Seo-Hyuk
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Natural Product Research Team, Gyeonggi Bio-Center, Gyeonggi Institute of Science and Technology Promotion, Suwon, 443-270, Republic of Korea.
authors.forename: Jin-Mo
authors.initials: JM
authors.lastname: Ku
authors.affiliation: Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Republic of Korea.
authors.forename: Jeong-Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Ki-Moon
authors.initials: KM
authors.lastname: Park
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Yongin, 446-701, Republic of Korea.
authors.forename: Joung-Woo
authors.initials: JW
authors.lastname: Hong
authors.affiliation: Department of Biomechatronic Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Geun Hyung
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 440-746, Republic of Korea. kwpark@skku.edu.
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Park
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D004149:Dioxoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects*; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D001572:Benzofurans; D050071:Bone Density Conservation Agents; D004149:Dioxoles; D005419:Flavonoids; D017395:Plasminogen Activator Inhibitor 1; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D016212:Transforming Growth Factor beta; D000469:Alkaline Phosphatase; C054989:sulfuretin
keywords: C3H10T1/2 cells; MC3T3-E1 cells; Osteoblast differentiation; Sulfuretin; TGF-beta