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DELETION OF AXIN GENE IN MOUSE ADIPOSE-DERIVED STEM CELLS (MASCS) PROMOTES OSTEOGENESIS
Presenter: Masakazu Hasegawa, MD, PhD
Co-Authors: Quarto N; Satoh K; Longaker MT
Stanford University

Introduction: Wnt pathway has been shown to be important for the osteogenic differentiation of mesenchymal stem cells, bone development, and bone homeostasis. However, the role of Wnt signaling in osteogenesis remains a controversial matter. We investigated how loss of Axin2, a negative regulator of Wnt signaling pathway, influences proliferation and osteogenic differentiation of mASCs.

Methods: Mouse ASCs were harvested from Axin2 null (Axin2-/-) transgenic mice and their corresponding background CD-1 mice. For the growth curve assay, cell counting was performed in triplicate. Cells were cultured in osteogenic differentiation media (ODM) with or without retinoic acid (RA) and with or without Wnt3a treatment. Mineralization of extracellular matrix was assessed by Alkaline phosphatase and Alizarin red staining. Analysis of genes associated with osteogenic differentiation (Runx2, Alpl) and BMP signaling (Bmp2, Bmp4, Smad1, Smad5) was performed by quantitative PCR (qPCR).

Results: A higher proliferative activity in Axin2-/- ASCs was revealed as compared to CD-1 ASCs. Axin2-/- ASCs showed more robust mineralization of the extracellular matrix than CD-1 ASCs in ODM with retinoic acid (RA). Interestingly, Axin2-/- ASCs in the absence of RA also underwent osteogenic differentiation, whereas, control WT ASCs failed. Furthermore, qPCR analysis showed that genes associated with BMP signaling, such as Bmp2, Bmp4, Smad1 and Smad5, were upregulated, specifically in Axin2-/- ASCs treated with Wnt3a.

Conclusion: Our results indicate that loss of a negative Wnt regulator, such as Axin2, promotes cell proliferation and higher osteogenic potential on Axin2-/- ASCs. Moreover, these results also suggest the occurrence of a cross talk between Wnt and BMP signaling which is responsible for the greater osteogenic potential of these cells.


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