Responsiveness of human bone marrow stromal cells to shear stress.
We examined the hypothesis that human mesenchymal stem cells detect physiological mechanical signals. Human bone marrow stromal cells (HBMSCs) were exposed to fluid shear stress of 12 dynes/cm(2) and analysed for their ability to express osteoblast-specific markers and associated signalling pathways. HBMSCs showed a significant increase in alkaline phosphatase (ALP) gene expression and a marked decrease in type I collagen, while no effect on Cbfa1/Runx2 was detected. This regulation is related to p38 and ERK1/2 activation, although the use of specific inhibitors to these two MAP kinases suggests that ALP mRNA induction is especially dependent on p38 activity, while type I collagen downregulation is ERK1/2-dependent. Interestingly, the expression of connexin43, which is involved in cell-to-cell communication of osteoblastic cells through gap junction formation, and its distribution through the cells, were modified by fluid flow (FF). HBMSCs are sensitive to shear stress and it appears essential to take their responsiveness into consideration before associating these regenerative cells with a bioactive biomaterial in a new bone tissue-engineering strategy.
Grellier
Maritie
M
INSERM, U577, Bordeaux and Université Victor Segalen Bordeaux 2, UMR-S577, Bordeaux, France. maritie.grellier@inserm.fr
Bareille
Reine
R
Bourget
Chantal
C
Amédée
Joëlle
J
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D024042:Collagen Type I / Q000235:genetics; D018031:Connexin 43 / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D017931:DNA Primers; D006801:Humans; D020935:MAP Kinase Signaling System; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D013314:Stress, Mechanical; D017154:Stromal Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism
D024042:Collagen Type I; D018031:Connexin 43; D050659:Core Binding Factor Alpha 1 Subunit; D017931:DNA Primers; D012333:RNA, Messenger; D000469:Alkaline Phosphatase