Vimentin contributes to changes in chondrocyte stiffness in osteoarthritis.

Prof. Dominik R Haudenschild, Ph.D.
Prof. Dominik R Haudenschild, Ph.D.
University of California Davis Medical Center
Arthritis Research
Sacramento, CA | United States
Nikolai Steklov
Nikolai Steklov
Shiley Center for Orthopaedic Research and Education at Scripps Clinic
San Diego | United States
Shawn P Grogan
Shawn P Grogan
1 Shiley Center for Orthopaedic Research and Education at Scripps Clinic
United States
Martin K Lotz
Martin K Lotz
The Scripps Research Institute
San Diego | United States

J Orthop Res 2011 Jan;29(1):20-5

Shiley Center for Orthopaedic Research and Education at Scripps Clinic, 11025 North Torrey Pines Road, La Jolla, California 92037, USA.

Actin and tubulin cytoskeletal components are studied extensively in chondrocytes, but less is known about vimentin intermediate filaments. In other cell types, vimentin is a determinant of cell stiffness and disruption of vimentin networks weakens the mechanical integrity of cells. Changes in vimentin organization correlate with osteoarthritis progression, but the functional consequences of these changes remain undetermined in chondrocytes. The objective of this study was to compare the contribution of vimentin to the mechanical stiffness of primary human chondrocytes isolated from normal versus osteoarthritic cartilage. Chondrocytes were embedded in alginate and vimentin networks disrupted with acrylamide. Constructs were imaged while subjected to 20% nominal strain on a confocal microscope stage, and the aspect ratios of approximately 1,900 cells were measured. Cytosolic stiffness was estimated with a finite element model, and live-cell imaging of GFP-vimentin was used to further analyze the nature of vimentin disruption. Vimentin in normal chondrocytes formed an inner cage-like network that was substantially stiffer than the rest of the cytosol and contributed significantly to overall cellular stiffness. Disruption of vimentin reduced stiffness approximately 2.8-fold in normal chondrocytes. In contrast, osteoarthritic chondrocytes were less stiff and less affected by vimentin disruption. This 3D experimental system revealed contributions of vimentin to chondrocyte stiffness previously not apparent, and correlated changes in vimentin-based chondrocyte stiffness with osteoarthritis.

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January 2011
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