title: SSH-BM-I, a tryptamine derivative, stimulates mineralization in terminal osteoblast differentiation but inhibits osteogenesis of pre-committed progenitor cells.
abstract: SSH-BM-I was synthesized from tryptamine by using a newly developed synthetic method, and it has structural similarity to bromomelatonin. Recently, it had been reported that SSH-BM-I increases osteoblasts in scales of gold fish. However, the effect of SSH-BM-I on osteoblast differentiation in mammalian cells has not yet been examined. Therefore, this study examined the effect of SSH-BM-I on osteoblast differentiation in mesenchymal progenitor-like cells and mature osteoblast-like cells. SSH-BM-I enhanced terminal osteoblast differentiation, as indicated by mineralization, which was accompanied by upregulation of the osteogenic marker genes bone sialoprotein (BSP) and osteocalcin (OC). However, in mesenchymal progenitor ROB-C26 cultures, no mineralized nodules were observed regardless of SSH-BM-I treatment, although BMP-2 was able to induce nodule formation in these cells. Furthermore, BMP-2-induced nodule formation was suppressed by SSH-BM-I treatment in ROB-C26 cultures. We further investigated the impact of the timing and duration of SSH-BM-I treatment on osteoblast differentiation. The effect of SSH-BM-I treatment on osteoblast differentiation of ROB-C26 in the presence of BMP-2 switches from negative to positive sometime between day 6 and 9, because SSH-BM-I treatment enhanced the formation of mineralized nodules when it was started on day 9, but suppressed nodule formation when it was started at day 6 or earlier. These results suggest that the stimulatory effects of SSH-BM-I on the formation of mineralized nodules depend on the degree of cell differentiation.
authors.affiliation: Department of Anatomy, Nihon University School of Dentistry, Tokyo 101-8310, Japan. mikami-t@dent.nihon-u.ac.jp
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Mikami
authors.forename: Masanori
authors.initials: M
authors.lastname: Somei
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects*; D017930:Genes, Reporter / Q000187:drug effects; D058574:Integrin-Binding Sialoprotein / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008550:Melatonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D051785:Smad Proteins / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D058574:Integrin-Binding Sialoprotein; D012333:RNA, Messenger; D051785:Smad Proteins; C528516:benzyl-tribromomelatonin; D015675:Osteocalcin; D008550:Melatonin