title: Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells.
abstract: Mesenchymal stem cells are pluripotent cells from bone marrow, which can be differentiated into the osteogenic, chondrogenic, and adipogenic lineages in vitro and are a source of cells in bone and cartilage tissue engineering. An improvement in current tissue-engineering protocols requires more detailed insight into the molecular cues that regulate the distinct steps of osteochondral differentiation. Because Wnt signaling has been widely implicated in mesenchymal differentiation, we analyzed the role of Wnt signaling in human mesenchymal stem cell (hMSC) biology by stimulation of the pathway with lithium chloride and Wnt3A-conditioned medium. We demonstrate a role for low levels of Wnt signaling in proliferation of uncommitted hMSCs and confirm that Wnt signaling controls osteoprogenitor proliferation. On the other hand, at high Wnt levels we observed a block in adipogenic differentiation and an increase in the expression of alkaline phosphatase, suggesting a role in the initiation of osteogenesis. The results of this study suggest that bone tissue engineering could benefit from the activation of critical levels of Wnt signaling at defined stages of differentiation. Moreover, our data suggest that hMSCs provide a valid in vitro model to study the role of Wnt signaling in mesenchymal biology.
authors.affiliation: Institute for Biomedical Technology, University of Twente, Twente, The Netherlands. j.deboer@tnw.utwente.nl
authors.forename: Jan
authors.initials: J
authors.lastname: De Boer
authors.forename: Hong Jun
authors.initials: HJ
authors.lastname: Wang
authors.forename: Clemens
authors.initials: C
authors.lastname: Van Blitterswijk
mesh_terms: D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins
chemical_list: D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins