title: 2,4,5-Trimethoxyldalbergiquinol promotes osteoblastic differentiation and mineralization via the BMP and Wnt/β-catenin pathway.
abstract: Dalbergia odorifera has been traditionally used as a medicine to treat many diseases. However, the role of 2,4,5-trimethoxyldalbergiquinol (TMDQ) isolated and extracted from D. odorifera in osteoblast function and the underlying molecular mechanisms remain poorly understood. The aim of this study was to investigate the effects and possible underlying mechanisms of TMDQ on osteoblastic differentiation of primary cultures of mouse osteoblasts as an in vitro assay system. TMDQ stimulated osteoblastic differentiation, as assessed by the alkaline phosphatase (ALP) activity, ALP staining, mineralized nodule formation, and the levels of mRNAs encoding the bone differentiation markers, including ALP, bone sialoprotein (BSP), osteopontin, and osteocalcin. TMDQ upregulated the expression of Bmp2 and Bmp4 genes, and increased the protein level of phospho-Smad1/5/8. Furthermore, TMDQ treatment showed the increased mRNA expression of Wnt ligands, phosphorylation of GSK3, and the expression of β-catenin protein. The TMDQ-induced osteogenic effects were abolished by Wnt inhibitor, Dickkopf-1 (DKK1), and bone morphogenetic protein (BMP) antagonist, noggin. TMDQ-induced runt-related transcription factor 2 (Runx2) expression was attenuatted by noggin and DKK1. These data suggest that TMDQ acts through the activation of BMP, Wnt/β-catenin, and Runx2 signaling to promote osteoblast differentiation, and we demonstrate that TMDQ could be a potential agent for the treatment of bone loss-associated diseases such as osteoporosis.
authors.affiliation: Department of Oral and Maxillofacial Pathology, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: H-M
authors.initials: HM
authors.lastname: Yun
authors.affiliation: Department of Oral and Maxillofacial Pathology, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: K-R
authors.initials: KR
authors.lastname: Park
authors.affiliation: Department of Pharmacy, Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea.
authors.forename: T H
authors.initials: TH
authors.lastname: Quang
authors.affiliation: Department of Pharmacy, Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Oh
authors.affiliation: Department of Pharmacy, College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju 361-763, Korea.
authors.forename: J T
authors.initials: JT
authors.lastname: Hong
authors.affiliation: Department of Pharmacy, Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Pathology, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: E-C
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D000840:Anisoles / Q000008:administration & dosage*; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D035782:Dalbergia / Q000737:chemistry*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D058574:Integrin-Binding Sialoprotein / Q000096:biosynthesis; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis; D053495:Osteopontin / Q000096:biosynthesis; D010024:Osteoporosis / Q000235:genetics / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis; D060449:Wnt Signaling Pathway / Q000187:drug effects; D000099176:Noggin Protein
chemical_list: D000469:Alkaline Phosphatase; D000840:Anisoles; D001559:Benzhydryl Compounds; D002352:Carrier Proteins; D058574:Integrin-Binding Sialoprotein; D036341:Intercellular Signaling Peptides and Proteins; D015675:Osteocalcin; D053495:Osteopontin; D010936:Plant Extracts; D012333:RNA, Messenger; D000099176:Noggin Protein; C000607363:2,4,5-trimethoxyldalbergiquinol; C501127:Dkk1 protein, mouse