Browsing by Subject "chondrocytes"

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    DIFFERENTIAL RHOA ACTIVITY IN CHONDROCYTES UNDER FLOW
    (Office of the Vice Chancellor for Research, 2012-04-13) Wan, Qiaoqiao; Yokota, Hiroki; Na, Sungsoo
    Mechanical force environment is a major factor that influences cellular homeostasis and remodeling. The prevailing wisdom in this field demon-strated that a threshold of mechanical forces or deformation was required to affect cell signaling. However, we hypothesized that RhoA activities can be either elevated or reduced by selecting different levels of shear stress inten-sities. To test this hypothesis, a fluorescence resonance energy transfer (FRET)-based approach was used. The result revealed that C28/I2 chondro-cytes exhibited an increase in RhoA activities in response to high shear stress (10 or 20 dyn/cm2), while they showed a decrease in their RhoA activ-ities to intermediate shear stress at 5 dyn/cm2. No changes were observed under low shear stress (2 dyn/ cm2). The observed two-level switch of RhoA activities was 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. Collectively, these results here suggest that intensities of shear stress are critical in differential activa-tion and inhibition of RhoA activities in chondrocytes.
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    Improved Tissue Repair in Articular Cartilage Defects in Vivo by rAAV-Mediated Overexpression of Human Fibroblast Growth Factor 2
    (Elsevier, 2005-08-01) Cucchiarini, Magali; Madry, Henning; Ma, Chunyan; Thurn, Tanja; Zurakowski, David; Menger, Michael D.; Kohn, Dieter; Trippel, Stephen B.; Terwilliger, Ernest F.; Orthopaedic Surgery, School of Medicine
    Therapeutic gene transfer into articular cartilage is a potential means to stimulate reparative activities in tissue lesions. We previously demonstrated that direct application of recombinant adeno-associated virus (rAAV) vectors to articular chondrocytes in their native matrix in situ as well as sites of tissue damage allowed for efficient and sustained reporter gene expression. Here we test the hypothesis that rAAV-mediated overexpression of fibroblast growth factor 2 (FGF-2), one candidate for enhancing the repair of cartilage lesions, would lead to the production of a biologically active factor that would facilitate the healing of articular cartilage defects. In vitro, FGF-2 production from an rAAV-delivered transgene was sufficient to stimulate chondrocyte proliferation over a prolonged period of time. In vivo, application of the therapeutic vector significantly improved the overall repair, filling, architecture, and cell morphology of osteochondral defects in rabbit knee joints. Differences in matrix synthesis were also observed, although not to the point of statistical significance. This process may further benefit from cosupplementation with other factors. These results provide a basis for rAAV application to sites of articular cartilage damage to deliver agents that promote tissue repair.