Leucine-rich amelogenin peptide induces osteogenesis by activation of the Wnt pathway.
We previously showed that one of the amelogenin splicing isoforms, Leucine-rich amelogenin peptide (LRAP), induced osteogenic differentiation of mouse embryonic stem cells; however, the signaling pathway(s) activated by LRAP remained unknown. Here, we demonstrated that the canonical Wnt/beta-catenin signaling is activated upon LRAP treatment, as evidenced by elevated beta-catenin level and increased Wnt reporter gene activity. Furthermore, a specific Wnt inhibitor sFRP-1 completely blocks the LRAP-mediated Wnt signaling. However, exogenous recombinant Wnt3a alone was less effective at osteogenic induction of mouse ES cells in comparison to LRAP. Using a quantitative real-time PCR array, we discovered that LRAP treatment up-regulated the expression of Wnt agonists and down-regulated the expression of Wnt antagonists. We conclude 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.
Warotayanont
Rungnapa
R
University of Southern California School of Dentistry, Center for Craniofacial Molecular Biology, 2250 Alcazar Street, Los Angeles, CA 90033, USA.
Frenkel
Baruch
B
Snead
Malcolm L
ML
Zhou
Yan
Y
D000818:Animals; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010012:Osteogenesis / Q000235:genetics; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
D003746:Dental Enamel Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C555510:WNT3A protein, human; C555511:Wnt3a protein, mouse; C067432:leucine-rich amelogenin peptide