title: The influence of Leucine-rich amelogenin peptide on MSC fate by inducing Wnt10b expression.
abstract: Amelogenin is the most abundant protein of the enamel organic matrix and is a structural protein indispensable for enamel formation. One of the amelogenin splicing isoforms, Leucine-rich Amelogenin Peptide (LRAP) induces osteogenesis in various cell types. Previously, we demonstrated that LRAP activates the canonical Wnt signaling pathway to induce osteogenic differentiation of mouse ES cells through the concerted regulation of Wnt agonists and antagonists. There is a reciprocal relationship between osteogenic and adipogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs). Wnt10b-mediated activation of canonical Wnt signaling has been shown to regulate mesenchymal stem cell fate. Using the bipotential bone marrow stromal cell line ST2, we have demonstrated that LRAP activates the canonical Wnt/β-catenin signaling pathway. A specific Wnt inhibitor sFRP-1 abolishes the effect of LRAP on the stimulation of osteogenesis and the inhibition of adipogenesis of ST2 cells. LRAP treatment elevates the Wnt10b expression level whereas Wnt10b knockdown by siRNA abrogates the effect of LRAP. We show here that LRAP promotes osteogenesis of mesenchymal stem cells at the expense of adipogenesis through upregulating Wnt10b expression to activate Wnt signaling.
authors.affiliation: Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA 90033, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wen
authors.forename: William P
authors.initials: WP
authors.lastname: Cawthorn
authors.forename: Ormond A
authors.initials: OA
authors.lastname: MacDougald
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Stupp
authors.forename: Malcolm L
authors.initials: ML
authors.lastname: Snead
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D019070:Cell Lineage / Q000187:drug effects*; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D003746:Dental Enamel Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin; C485539:Sfrp1 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C102068:Wnt10b protein, mouse; C067432:leucine-rich amelogenin peptide