title: Piceatannol stimulates osteoblast differentiation that may be mediated by increased bone morphogenetic protein-2 production.
abstract: Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine. By means of alkaline phosphatase activity and osteocalcin enzyme-linked immunosorbent assay (ELISA), we have shown that piceatannol exhibits a significant induction of differentiation in immortalized fetal osteoblasts (hFOB), and osteosarcoma cells (MG-63). Alkaline phosphatase and osteocalcin are phenotypic markers for early-stage differentiated osteoblasts and terminally differentiated osteoblasts, respectively, our results indicate that piceatannol stimulate osteoblast differentiation at various stages (from maturation to terminally differentiated osteoblasts). Induction of differentiation by piceatannol was associated with increased bone morphogenetic protein-2 (BMP-2) production. Addition of purified BMP-2 protein did not increase the upregulation of alkaline phosphatase activity and osteocalcin secretion by piceatannol, whereas the BMP-2 antagonist noggin blocked piceatannol and BMP-2-mediated alkaline phosphatase activity, and osteocalcin secretion enhancement, indicating that BMP-2 production is required in piceatannol-mediated osteoblast maturation and differentiation. In conclusion, piceatannol increased BMP-2 synthesis, and this effect may contribute to its action on the induction of osteoblasts maturation and differentiation, followed by an increase of bone mass. Decreases in new bone formation, followed by estrogen deficiency or various pathologic factors, may contribute to the mechanisms involved in postmenopausal osteoporosis.
authors.affiliation: Cell Biology Laboratory, Department of Biotechnology, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.
authors.forename: Jiunn-Kae
authors.initials: JK
authors.lastname: Chang
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Hsu
authors.forename: I-Chun
authors.initials: IC
authors.lastname: Teng
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Kuo
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002113:Calcification, Physiologic / Q000187:drug effects; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects; D000099176:Noggin Protein
chemical_list: D000469:Alkaline Phosphatase; D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D024042:Collagen Type I; D015675:Osteocalcin; D012333:RNA, Messenger; D013267:Stilbenes; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525718:BMP2 protein, human; C041525:3,3',4,5'-tetrahydroxystilbene