title: Effects of vimentin disruption on the mechanoresponses of articular chondrocyte.
abstract: Human articular cartilage is subjected to repetitive mechanical loading during life time. As the only cellular component of articular cartilage, chondrocytes play a key role in the mechanotransduction within this tissue. The mechanoresponses of chondrocytes are largely determined by the cytoskeleton. Vimentin intermediate filaments, one of the major cytoskeletal components, have been shown to regulate chondrocyte phenotype. However, the contribution of vimentin in chondrocyte mechanoresponses remains less studied. In this study, we seeded goat articular chondrocytes on a soft polyacrylamide gel, and disrupted the vimentin cytoskeleton using acrylamide. Then we applied a transient stretch or compression to the cells, and measured the changes of cellular stiffness and traction forces using Optical Magnetic Twisting Cytometry and Traction Force Microscopy, respectively. In addition, to study the effects of vimentin disruption on the intracellular force generation, we treated the cells with a variety of reagents that are known to increase or decrease cytoskeletal tension. We found that, after a compression, the contractile moment and cellular stiffness were not affected in untreated chondrocytes, but were decreased in vimentin-disrupted chondrocytes; after a stretch, vimentin-disrupted chondrocytes showed a lower level of fluidization-resolidification response compared to untreated cells. Moreover, vimentin-disrupted chondrocytes didn't show much difference to control cells in responding to reagents that target actin and ROCK pathway, but showed a weaker response to histamine and isoproterenol. These findings confirmed chondrocyte vimentin as a major contributor in withstanding compressive loading, and its minor role in regulating cytoskeletal tension.
authors.affiliation: Center for Joint Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Center for Joint Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Yin
authors.affiliation: Center for Joint Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Xiongbo
authors.initials: X
authors.lastname: Song
authors.affiliation: Center for Joint Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Center for Joint Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ren
authors.affiliation: Center for Joint Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Gong
authors.affiliation: Center for Joint Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Fuyou
authors.initials: F
authors.lastname: Wang
authors.affiliation: Center for Joint Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, PR China. Electronic address: jointsurgery@163.com.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D019245:Compressive Strength / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology*; D055119:Elastic Modulus / Q000502:physiology; D006041:Goats; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods*; D013314:Stress, Mechanical; D013718:Tensile Strength / Q000502:physiology; D014746:Vimentin / Q000502:physiology*
chemical_list: D014746:Vimentin
keywords: Articular chondrocyte; Cell mechanics; Compression; Stretch; Vimentin