title: Differential activation and inhibition of RhoA by fluid flow induced shear stress in chondrocytes.
abstract: Physical force environment is a major factor that influences cellular homeostasis and remodelling. It is not well understood, however, as a potential role of force intensities in the induction of cellular mechanotransduction. Using a fluorescence resonance energy transfer-based approach, we asked whether activities of GTPase RhoA in chondrocytes are dependent on intensities of flow-induced shear stress. We hypothesized that RhoA activities can be either elevated or reduced by selecting different levels of shear-stress intensities. The result indicates that C28/I2 chondrocytes have increased RhoA activities in response to high shear stress (10 or 20 dyn/cm(2) ), whereas a decrease in activity was seen with an intermediate shear stress of 5 dyn/cm(2) . No changes were seen under low shear stress (2 dyn/cm(2) ). The observed two-level switch of RhoA activities is closely linked to the shear-stress-induced alterations in actin cytoskeleton and traction forces. In the presence of constitutively active RhoA (RhoA-V14), intermediate shear stress suppressed RhoA activities, while high shear stress failed to activate them. In chondrocytes, expression of various metalloproteinases is, in part, regulated by shear and normal stresses through a network of GTPases. Collectively, the data suggest that intensities of shear stress are critical in differential activation and inhibition of RhoA activities in chondrocytes.
authors: Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, 723 West Michigan Street, Indianapolis, IN 46202, USA.
authors: Qiaoqiao
authors: Q
authors: Wan
authors: Seung Joon
authors: SJ
authors: Kim
authors: Hiroki
authors: H
authors: Yokota
authors: Sungsoo
authors: S
authors: Na
mesh_terms: D008841:Actin Cytoskeleton; D019902:Chondrocytes / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D013314:Stress, Mechanical; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020742:rhoA GTP-Binding Protein