First published online February 4, 2009
Journal of Cell Science 122, 401e (2009)
© The Company of Biologists Limited
Osteogenesis goes with the flow
There is mounting evidence that the mechanical microenvironment within a tissue can influence stem-cell fate; much remains unknown, however, about how particular mechanical signals are transduced. On page 546, Emily Arnsdorf and colleagues investigate how one such signal – oscillatory fluid flow (which promotes osteogenesis in mature bone) – determines the fate of mesenchymal stem cells. Using C3H10T1/2 progenitor cells as a model, the authors analyse the effect of oscillatory fluid flow on the expression of the transcription factors Runx2, PPAR
and SOX9 (markers of osteogenic, adipogenic and chondrogenic differentiation, respectively). They show that all three proteins are upregulated, as are the GTPase RhoA and its effector ROCKII (which probably enhance tension in the actin cytoskeleton). In addition, chemical activation of RhoA acts additively with flow to upregulate expression of Runx2, whereas disruption of the actin cytoskeleton downregulates flow-induced Runx2 expression. Lastly, they show that – unlike Runx2 – SOX9 and PPAR
are upregulated by actin-cytoskeleton disruption in the absence of flow, and RhoA activation also downregulates PPAR
expression. They conclude, therefore, that oscillatory fluid flow regulates the osteogenic differentiation of progenitor cells via the RhoA-ROCKII pathway.

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Related articles in JCS:
- Mechanically induced osteogenic differentiation – the role of RhoA, ROCKII and cytoskeletal dynamics
- Emily J. Arnsdorf, Padmaja Tummala, Ronald Y. Kwon, and Christopher R. Jacobs
JCS 2009 122: 546-553.
[Abstract]
[Full Text]