Vimentin contributes to changes in chondrocyte stiffness in osteoarthritis

Authors

  • Dominik R. Haudenschild,

    Corresponding author
    1. Shiley Center for Orthopaedic Research and Education at Scripps Clinic, 11025 North Torrey Pines Road, La Jolla, California 92037
    2. The Scripps Research Institute, Division of Arthritis Research, 10550 North Torrey Pines Road, La Jolla, California 92037
    Current affiliation:
    1. UC Davis Medical Center, Department of Orthopaedic Surgery, 4635 Second Avenue Room 2000, Sacramento, CA 95817, USA.
    • Shiley Center for Orthopaedic Research and Education at Scripps Clinic, 11025 North Torrey Pines Road, La Jolla, California 92037. T: 916-734-5015; F: 916-734-5750.
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  • Jianfen Chen,

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

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

    1. Shiley Center for Orthopaedic Research and Education at Scripps Clinic, 11025 North Torrey Pines Road, La Jolla, California 92037
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  • Shawn P. Grogan,

    1. Shiley Center for Orthopaedic Research and Education at Scripps Clinic, 11025 North Torrey Pines Road, La Jolla, California 92037
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  • Martin K. Lotz,

    1. The Scripps Research Institute, Division of Arthritis Research, 10550 North Torrey Pines Road, La Jolla, California 92037
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  • Darryl D. D'Lima

    1. Shiley Center for Orthopaedic Research and Education at Scripps Clinic, 11025 North Torrey Pines Road, La Jolla, California 92037
    2. The Scripps Research Institute, Division of Arthritis Research, 10550 North Torrey Pines Road, La Jolla, California 92037
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Abstract

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. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:20–25, 2011

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