Wnt signaling inhibits osteogenic differentiation of human mesenchymal stem cells

Jan De Boer, Ramakrishnaiah Siddappa, Claudia Gaspar, Aart Van Apeldoorn, Ricardo Fodde, Clemens Van Blitterswijk

Research output: Contribution to journalArticleAcademicpeer-review

183 Citations (Scopus)

Abstract

Human mesenchymal stem cells (hMSCs) from the bone marrow represent a potential source of pluripotent cells for autologous bone tissue engineering. We previously discovered that over activation of the Wnt signal transduction pathway by either lithium or Wnt3A stimulates hMSC proliferation while retaining pluripotency. Release of Wnt3A or lithium from porous calcium phosphate scaffolds, which we use for bone tissue engineering, could provide a mitogenic stimulus to implanted hMSCs. To define the proper release profile, we first assessed the effect of Wnt over activation on osteogenic differentiation of hMSCs. Here, we report that both lithium and Wnt3A strongly inhibit dexamethasone-induced expression of the osteogenic marker alkaline phosphatase (ALP). Moreover, lithium partly inhibited mineralization of hMSCs whereas Wnt3A completely blocked it. Time course analysis during osteogenic differentiation revealed that 4 days of Wnt3A exposure before the onset of mineralization is sufficient to block mineralization completely. Gene expression profiling in Wnt3A and lithium-exposed hMSCs showed that many osteogenic and chondrogenic markers, normally expressed in proliferating hMSCs, are downregulated upon Wnt stimulation. We conclude that Wnt signaling inhibits dexamethasone-induced osteogenesis in hMSCs. In future studies, we will try to limit release of lithium or Wnt3A from calcium phosphate scaffolds to the proliferative phase of osteogenesis.

Original languageEnglish
Pages (from-to)818-826
Number of pages9
JournalBone
Volume34
Issue number5
DOIs
Publication statusPublished - 1 May 2004
Externally publishedYes

Keywords

  • Human mesenchymal stem cells
  • Micro-array
  • Osteogenesis
  • Tissue engineering
  • Wnt signaling

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