title: Wnt5a Supports Osteogenic Lineage Decisions in Embryonic Stem Cells.
abstract: The specification of pluripotent stem cells into the bone-forming osteoblasts has been explored in a number of studies. However, the current body of literature has yet to adequately address the role of Wnt glycoproteins in the differentiation of pluripotent stem cells along the osteogenic lineage. During mouse embryonic stem cell (ESC) in vitro osteogenesis, the noncanonical WNT5a is expressed early on. Cells either sorted by their positive WNT5a expression or when supplemented with recombinant WNT5a (rWNT5a) during a 2-day window showed significantly enhanced osteogenic yield. Mechanistically, rWNT5a supplementation upregulated protein kinase C (PKC), calcium/calmodulin-dependent kinase II (CamKII) and c-Jun N-terminal kinase (JNK) activity while antagonizing the key effector of canonical Wnt signaling: β-catenin. Conversely, when recombinant WNT3a (rWNT3a) or other positive regulators of β-catenin were employed during this same time window there was a decrease in osteogenic marker expression. However, if rWNT3a was supplemented during a time window following rWNT5a treatment, osteogenic differentiation was enhanced both in murine and human ESCs. Elucidating the role of these WNT ligands in directing the early stages of osteogenesis has the potential to considerably improve tissue engineering protocols and applications for regenerative medicine.
authors.affiliation: 1 Department of Cell Biology & Neuroscience, Stem Cell Center, College of Natural and Agricultural Sciences, University of California Riverside , Riverside, California.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Keller
authors.affiliation: 2 Applied Stem Cell Technologies Unit, Department for Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology , Leipzig, Germany .
authors.forename: Huawen
authors.initials: H
authors.lastname: Ding
authors.affiliation: 1 Department of Cell Biology & Neuroscience, Stem Cell Center, College of Natural and Agricultural Sciences, University of California Riverside , Riverside, California.
authors.forename: Rudy
authors.initials: R
authors.lastname: Tieu
authors.affiliation: 1 Department of Cell Biology & Neuroscience, Stem Cell Center, College of Natural and Agricultural Sciences, University of California Riverside , Riverside, California.
authors.forename: Nicole R L
authors.initials: NR
authors.lastname: Sparks
authors.affiliation: 1 Department of Cell Biology & Neuroscience, Stem Cell Center, College of Natural and Agricultural Sciences, University of California Riverside , Riverside, California.
authors.forename: Devon D
authors.initials: DD
authors.lastname: Ehnes
authors.affiliation: 1 Department of Cell Biology & Neuroscience, Stem Cell Center, College of Natural and Agricultural Sciences, University of California Riverside , Riverside, California.|2 Applied Stem Cell Technologies Unit, Department for Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology , Leipzig, Germany .
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Zur Nieden
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology; D010012:Osteogenesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D000071818:Wnt-5a Protein / Q000378:metabolism*; D060509:Wnt3A Protein / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein; D051176:beta Catenin; D002762:Cholecalciferol